DM 疾病标记 1875 - 8630 0278 - 0240 Hindawi 10.1155 / 2021/9958909 9958909 研究文章 的角色ssDNA的无创性诊断指标和肝细胞癌的预后:一个探索性研究 1 Yiqiu 2 https://orcid.org/0000 - 0001 - 8958 - 7861 丹丹 2 军军 2 3 国荣 4 https://orcid.org/0000 - 0002 - 3802 - 111 x Xuewen 5 El-Khazragy Nashwa 1 临床实验室的部门 南京医科大学附属无锡人民医院 庆阳路299号 江苏无锡214023 中国 njmu.edu.cn 2 临床实验室的部门 的附属无锡第二人民医院南京医科大学 68年中山路 江苏无锡214002 中国 njmu.edu.cn 3 感染管理系 南京医科大学附属苏州医院 Guangji路68号 江苏苏州215008 中国 4 临床实验室医学系 苏州第九医院隶属于苏州大学 Ludang路2666号 江苏苏州215200 中国 5 研究与开发 江苏元生物科技有限公司 有限公司 Xingpu路333号 江苏苏州215000 中国 2021年 5 8 2021年 2021年 19 3 2021年 29日 6 2021年 20. 7 2021年 5 8 2021年 2021年 版权©2021齐赵et al。 这是一个开放的文章在知识共享归属许可下发布的,它允许无限制的使用,分布和繁殖在任何媒介,提供最初的工作是正确的引用。

背景和目的。这个探索性研究探索了单链DNA (ssDNA)对肝细胞癌(HCC)诊断和预后。 方法。这项前瞻性研究招收了102名新诊断HCC患者21例肝硬化,与慢性肝炎20,284与非疾病,45健康个体的附属无锡第二人民医院南京医科大学(2018年五月-十月)。ssDNA提取使用磁珠和量化使用量子位ssDNA化验。ssDNA水平相比在疾病组和肝细胞癌与non-HCC。接受者操作特征曲线(ROC)被用来确定ssDNA的诊断价值。可切除的肝细胞癌患者,ssDNA和 α胎蛋白(法新社)水平测定在随访中并与肝癌复发被成像。 结果。在肝细胞癌中位数ssDNA水平高于健康人,肝硬化和慢性肝炎(中位数,23.20和9.36,9.64,和9.76 ng / μL,分别 P < 0.001 )。ssDNA水平在肝细胞癌高于肝硬化和慢性肝炎(两者都是 P < 0.001 );没有ssDNA水平差异健康对照组和肝硬化患者( P = 0.15 )或慢性肝病( P = 0.39 )。曲线下的面积的ssDNA HCC诊断为0.909(95%置信区间:0.879—-0.933)。ssDNA水平下降了3.19倍( P < 0.001 肝细胞癌切除后)。在六个病人,ssDNA水平增加约3 - 6个月复发前被法新社和成像检测。 结论。ssDNA可能是一种无创性肝细胞癌诊断和预后指标。ssDNA最终能补充AFP水平和成像,但是验证性研究是必要的。 1。介绍<gydF4y2Ba/title> <p>肝细胞癌(HCC)是第五位最常见的癌症和癌症相关的死亡率在世界范围内的第三更重要的原因(<gydF4y2Baxref ref-type="bibr" rid="B1"> 1<gydF4y2Ba/xref>]。肝癌的主要病因是慢性乙肝和丙肝,在像中国这样的国家流行,导致肝癌的发病率高(<gydF4y2Baxref ref-type="bibr" rid="B2"> 2<gydF4y2Ba/xref>),40.0 15.3每100000男性和100000女性(<gydF4y2Baxref ref-type="bibr" rid="B3"> 3<gydF4y2Ba/xref>]。肝癌的发展由于肝脏损伤和/或炎症导致肝纤维化、肝硬化,异常的肝细胞再生,和肿瘤出现前的病变的形成<gydF4y2Baxref ref-type="bibr" rid="B4"> 4<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B5"> 5<gydF4y2Ba/xref>]。否则,特定的发病机理取决于特定的病因。Hepatotropic病毒引起炎症、细胞损伤,增加细胞营业额、纤维化和肝硬化(<gydF4y2Baxref ref-type="bibr" rid="B5"> 5<gydF4y2Ba/xref>]。酒精肝是由于乙醇代谢和炎症与氧化应激相关的(<gydF4y2Baxref ref-type="bibr" rid="B5"> 5<gydF4y2Ba/xref>]。非酒精性脂肪肝炎与氧化应激有关,胰岛素抵抗,adipocytokine功能紊乱和细胞增生导致致癌作用[<gydF4y2Baxref ref-type="bibr" rid="B5"> 5<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>甲胎蛋白(AFP)是肝细胞癌诊断的生物标志物和监控,并增加AFP水平可以发现在39% -65%的肝癌患者,但很多肝癌患者AFP水平较低(例如,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng / mL) [<gydF4y2Baxref ref-type="bibr" rid="B6"> 6<gydF4y2Ba/xref>]。因此,有必要对互补生物标志物。法新社的组合和其他传统肿瘤标记物(着)对肝癌的诊断是一个可能的策略<gydF4y2Baxref ref-type="bibr" rid="B7"> 7<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B9"> 9<gydF4y2Ba/xref>]。新的生物标志物如高尔基蛋白73 (GP73) (<gydF4y2Baxref ref-type="bibr" rid="B10"> 10<gydF4y2Ba/xref>),glypican-3 (GPC-3) [<gydF4y2Baxref ref-type="bibr" rid="B11"> 11<gydF4y2Ba/xref>),和小分子核糖核酸<gydF4y2Baxref ref-type="bibr" rid="B12"> 12<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B14"> 14<gydF4y2Ba/xref>)正在接受调查,但低敏感性和/或特异性肝癌限制他们的应用程序在临床实践<gydF4y2Baxref ref-type="bibr" rid="B10"> 10<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B14"> 14<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>游离DNA (cfDNA)主要来自于凋亡和坏死细胞和包含完整的遗传信息的组织来源。cfDNA被建议作为一种动态实时标记肝癌患者负担各种治疗和作为一个可能的方法检测肿瘤突变(<gydF4y2Baxref ref-type="bibr" rid="B15"> 15<gydF4y2Ba/xref>]。研究cfDNA HCC诊断重点检测肿瘤突变和甲基化信息使用各种技术,但是这些技术是昂贵的,结果是矛盾的<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B20"> 20.<gydF4y2Ba/xref>]。先前的研究表明,定量测定cfDNA可能对肝细胞癌的诊断和预后价值(<gydF4y2Baxref ref-type="bibr" rid="B21"> 21<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B22"> 22<gydF4y2Ba/xref>),但cfDNA不提供信息的定量分析肝细胞癌的生物学和分子特征。虽然在HCC cfDNA定量分析的有效性是有争议的,它有优点例如简单,快速,便宜的(<gydF4y2Baxref ref-type="bibr" rid="B23"> 23<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B24"> 24<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>当考虑AFP-negative HCC的高比例<gydF4y2Baxref ref-type="bibr" rid="B6"> 6<gydF4y2Ba/xref>)和cfDNA和肝细胞癌之间的联系(<gydF4y2Baxref ref-type="bibr" rid="B21"> 21<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B22"> 22<gydF4y2Ba/xref>),cfDNA可以用来检测肝癌AFP-negative患者。cfDNA由单链DNA双链DNA (dsDNA)和(ssDNA)。先前的研究的定量变化cfDNA关注dsDNA。ssDNA比dsDNA[复制压力的早期标志<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B27"> 27<gydF4y2Ba/xref>]。在细胞复制高压力和不受控制的复制(如肿瘤细胞)、停滞或崩溃的复制叉由于酶不协调导致ssDNA形成和释放通过凋亡细胞(<gydF4y2Baxref ref-type="bibr" rid="B25"> 25<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B26"> 26<gydF4y2Ba/xref>]。此外,等离子体ssDNA水平远高于dsDNA [<gydF4y2Baxref ref-type="bibr" rid="B23"> 23<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B24"> 24<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>因此,可以假设等离子ssDNA是肝细胞癌的一个标志。本探索性研究旨在探索ssDNA对肝细胞癌的诊断和预后价值。<gydF4y2Ba/p> </sec> <sec id="sec2"> <title>2。材料和方法<gydF4y2Ba/title> <sec id="sec2.1"> <title>2.1。研究设计和病人<gydF4y2Ba/title> <p>这个未来的探索性研究了新诊断HCC患者(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)、肝硬化(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 21<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>),慢性肝炎(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>),而非条件(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 284年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)附属无锡第二人民医院南京医科大学在2018年5月和10月之间。他们确定了基于症状,影像学表现,活检,着包括法新社和癌抗原(CA)后,和其他血清标记(<gydF4y2Baxref ref-type="bibr" rid="B28"> 28<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B30"> 30.<gydF4y2Ba/xref>]。给定的病人包括只有一次在第一次入学。这项研究是伦理委员会批准的附属无锡第二人民医院南京医科大学(# Y-25)。参与者提供书面知情同意之前,任何研究过程。<gydF4y2Ba/p> <p>健康的人(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M11"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 45<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)注册时参观了医院例行检查。入选标准并没有肿瘤和肝标记高于正常的上限和正常体检(计算机断层扫描(CT)、上消化道内窥镜检查和腹部超声)。排除标准(1)< 30岁,(2)以前的治疗(大手术、化疗、内分泌治疗或慢性任何药物治疗),(3)良性肿瘤,(4)慢性炎性疾病(糖尿病、心血管疾病、或风湿性疾病),或(5)任何自身免疫性疾病。<gydF4y2Ba/p> <p>分析肝脏ssDNA水平的条件下,参与者被分组为肝细胞癌(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M12"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)、肝硬化(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M13"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 21<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>),慢性肝炎(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M14"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>和健康的人<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M15"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 45<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。诊断价值分析,参与者分组作为肝细胞癌(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M16"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)和non-HCC (<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M17"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 325年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)组。可切除的肝细胞癌被定义为任何被医生判定为可切除的肝细胞癌专业肿瘤肝脏手术根据儿童分类(<gydF4y2Baxref ref-type="bibr" rid="B28"> 28<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B30"> 30.<gydF4y2Ba/xref>]。AFP-positive HCC患者被定义为<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M18"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng / mL [<gydF4y2Baxref ref-type="bibr" rid="B31"> 31日<gydF4y2Ba/xref>]。<gydF4y2Ba/p> </sec> <sec id="sec2.2"> <title>2.2。血液采样<gydF4y2Ba/title> <p>禁食外周血采样任何治疗之前使用4毫升EDTA真空管(BD生物科学,富兰克林湖,新泽西,美国)和4毫升凝胶procoagulation真空管(BD生物科学,富兰克林湖,新泽西,美国)。可切除的肝细胞癌患者,血液样本在3天,14日,手术后30、60。切除标本检查。肝癌的临床或病理分期进行节点根据肿瘤转移(TNM)分类<gydF4y2Baxref ref-type="bibr" rid="B32"> 32<gydF4y2Ba/xref>]。肿瘤大小是根据响应评估标准在实体瘤(RECIST) 1.1 (<gydF4y2Baxref ref-type="bibr" rid="B33"> 33<gydF4y2Ba/xref>]。腹部和盆腔CT进行手术后60天(化疗前)和作为RECIST基线评估。<gydF4y2Ba/p> <p>肝细胞癌患者和ssDNA<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M19"> <mml:mtext> 水平<gydF4y2Ba/mml:mtext> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 12.36<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L彻底切除后,CT扫描和血液采样每3个月进行。疾病反应是评估根据RECIST 1.1版本:完全缓解(CR),部分响应(PR),进步的疾病(PD)和稳定的疾病(SD)。<gydF4y2Ba/p> </sec> <sec id="sec2.3"> <title>2.3。ssDNA量化<gydF4y2Ba/title> <p>血液样本图1 h内处理。等离子体是通过离心<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M20"> <mml:mn> 1900年<gydF4y2Ba/mml:mn> <mml:mo> ×<gydF4y2Ba/mml:mo> <mml:mtext> g<gydF4y2Ba/mml:mtext> </mml:math> </inline-formula>10分钟。等离子体又离心机<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M21"> <mml:mn> 16000年<gydF4y2Ba/mml:mn> <mml:mo> ×<gydF4y2Ba/mml:mo> <mml:mtext> g<gydF4y2Ba/mml:mtext> </mml:math> </inline-formula>10分钟。收集到的等离子体是储存在-80°C。<gydF4y2Ba/p> <p>cfDNA提取进行了使用DNA提取游离工具包(元生物科技、江苏、中国),基于磁珠的方法和根据制造商的指示,2小时内的样本解冻。简单地说,1毫升的裂解吸附剂和12.5<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L蛋白酶K被添加到0.5毫升的等离子体和离心机1500 rpm和60°C 10分钟。然后,10<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L(磁珠添加和离心机1500 rpm在室温下10分钟。磁珠磁性框架上被抓获。cfDNA是筛选了25<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L(洗脱缓冲B和储存在-20°C。混合等离子体作为质量控制监督提取效率的变化。<gydF4y2Ba/p> <p>使用5 ssDNA水平测定<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L(每个样本和量子位ssDNA分析工具包(美国生活技术,卡尔斯巴德,CA),根据制造商的指示。在1的量化ssDNA进行<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L模式利用量子位3.0荧光计(美国生活技术,卡尔斯巴德,CA)。两个对每个样本进行复制。的变异系数ssDNA浓度质量控制必须小于5%。<gydF4y2Ba/p> </sec> <sec id="sec2.4"> <title>2.4。血清AFP、CA19-9 CA12-5和CEA<gydF4y2Ba/title> <p>血清AFP、CA19-9 CA12-5和癌胚抗原(CEA)水平测定2 h内使用商业测试工具(罗氏诊断、巴塞尔、瑞士)Cobas e601分析仪(罗氏诊断、巴塞尔、瑞士),与正常的上限9 ng / mL, 35 U /毫升,35 U /毫升,分别和5 ng / mL。<gydF4y2Ba/p> </sec> <sec id="sec2.5"> <title>2.5。统计分析<gydF4y2Ba/title> <p>病人的特点,提出了根据BCLC截止点的分类(<gydF4y2Baxref ref-type="bibr" rid="B34"> 34<gydF4y2Ba/xref>]。使用Mann-Whitney连续变量进行了分析<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M22"> <mml:mi> U<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>以及克鲁斯卡尔-沃利斯检验。成对使用Wilcoxon连续变量进行了分析测试。分类变量进行了分析使用卡方测试或与连续性校正卡方测试。接受者操作特征(ROC)曲线分析是用来分析ssDNA的诊断价值。价值最大的Youden指数被选为最优截止值。一个值大于或等于截止值被认为是积极的,和较小的值被认为是消极的。ssDNA水平和肿瘤大小之间的关系进行了分析,线性回归。<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M23"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>值< 0.05被认为是具有统计学意义。ROC曲线下的面积(AUC)据报道使用双面的95%可信区间(CI)。使用SPSS 16.0统计分析(美国、IBM、纽约Armonk)。<gydF4y2Ba/p> </sec> </sec> <sec id="sec3"> <title>3所示。结果<gydF4y2Ba/title> <sec id="sec3.1"> <title>3.1。研究对象的特点<gydF4y2Ba/title> <p>最后,472名受试者:AFP-negative HCC患者61,41 AFP-positive HCC患者,21与肝硬化,慢性肝炎20,28日与冠心病、34和自身免疫性疾病,与糖尿病20,53岁,肺癌,43与结直肠肿瘤,30胃与十二指肠的肿瘤,与头部和颈部肿瘤,16 5与泌尿系肿瘤,与食管肿瘤19,11与妇科肿瘤,9与胰腺癌,并与其他肿瘤16;45健康人也参加。102例肝细胞癌患者中,37个阶段我,42阶段II, iii iv和23个阶段。102名患者中,62人可切除的肝细胞癌(表<gydF4y2Baxref rid="tab1" ref-type="table"> 1<gydF4y2Ba/xref>),13例(12.8%)有淋巴结转移,9例(8.8%)有远处转移,76(74.5%)乙型肝炎病毒(HBV)阳性。<gydF4y2Ba/p> <table-wrap id="tab1"> <label>表1<gydF4y2Ba/label> <p>ssDNA关系水平和102例肝细胞癌患者的临床特征。<gydF4y2Ba/p> <table> <thead> <tr> <th align="left">特征<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M24"> <mml:mi> n<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>(%)<gydF4y2Ba/th> <th align="center">(ng / ssDNA水平<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L),中等(差)<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M25"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula></th> </tr> </thead> <tbody> <tr> <td align="left">所有<gydF4y2Ba/td> <td align="center">102 (100)<gydF4y2Ba/td> <td align="center">23.20 (16.86 - -44.40)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left"> <italic> 年龄(年)<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">≤60<gydF4y2Ba/td> <td align="center">33 (32.4)<gydF4y2Ba/td> <td align="center">21.20 (15.75 - -58.60)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">60 +<gydF4y2Ba/td> <td align="center">69 (67.6)<gydF4y2Ba/td> <td align="center">23.80 (18.05 - -39.84)<gydF4y2Ba/td> <td align="center">0.99<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 性<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">男性<gydF4y2Ba/td> <td align="center">77 (75.5)<gydF4y2Ba/td> <td align="center">23.80 (17.30 - -51.69)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">女<gydF4y2Ba/td> <td align="center">25 (24.5)<gydF4y2Ba/td> <td align="center">21.20 (15.75 - -37.87)<gydF4y2Ba/td> <td align="center">0.42<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> AFP水平<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">AFP-negative肝癌<gydF4y2Ba/td> <td align="center">61 (59.8)<gydF4y2Ba/td> <td align="center">20.20 (15.88 - -50.33)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M26"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>纳克/毫升<gydF4y2Ba/td> <td align="center">41 (40.2)<gydF4y2Ba/td> <td align="center">31.50 (18.69 - -37.58)<gydF4y2Ba/td> <td align="center">0.33<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 肝硬化<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">Cirrhosis-negative肝癌<gydF4y2Ba/td> <td align="center">47 (46.1)<gydF4y2Ba/td> <td align="center">26.64 (16.34 - -52.35)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">Cirrhosis-positive肝癌<gydF4y2Ba/td> <td align="center">55 (43.9)<gydF4y2Ba/td> <td align="center">21.46 (18.02 - -40.91)<gydF4y2Ba/td> <td align="center">0.64<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 肿瘤大小(毫米)(肿瘤)之和<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">≤20<gydF4y2Ba/td> <td align="center">30 (29.4)<gydF4y2Ba/td> <td align="center">19.60 (15.20 - -48.60)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">20 - 50<gydF4y2Ba/td> <td align="center">35 (34.3)<gydF4y2Ba/td> <td align="center">19.20 (15.83 - -47.55)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">≥50<gydF4y2Ba/td> <td align="center">37 (36.3)<gydF4y2Ba/td> <td align="center">30.80 (20.07 - -38.39)<gydF4y2Ba/td> <td align="center">0.13<gydF4y2Basup>b<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 肿瘤阶段(TNM)<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">我<gydF4y2Ba/td> <td align="center">37 (36.3)<gydF4y2Ba/td> <td align="center">18.93 (15.98 - -34.70)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">二世<gydF4y2Ba/td> <td align="center">42 (41.2)<gydF4y2Ba/td> <td align="center">22.63 (16.86 - -49.80)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">iii iv<gydF4y2Ba/td> <td align="center">23日(22.6)<gydF4y2Ba/td> <td align="center">34.80 (22.25 - -54.58)<gydF4y2Ba/td> <td align="center">0.02<gydF4y2Basup>b<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 切除肝癌<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">是的<gydF4y2Ba/td> <td align="center">62 (60.8)<gydF4y2Ba/td> <td align="center">19.70 (15.80 - -37.80)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">没有<gydF4y2Ba/td> <td align="center">40 (39.2)<gydF4y2Ba/td> <td align="center">28.50 (19.34 - -54.05)<gydF4y2Ba/td> <td align="center">0.02<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 淋巴结转移<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">是的<gydF4y2Ba/td> <td align="center">13 (12.8)<gydF4y2Ba/td> <td align="center">48.60 (19.65 - -60.60)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">没有<gydF4y2Ba/td> <td align="center">89 (87.2)<gydF4y2Ba/td> <td align="center">21.20 (16.85 - -38.39)<gydF4y2Ba/td> <td align="center">0.09<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 远处转移<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">是的<gydF4y2Ba/td> <td align="center">9 (8.8)<gydF4y2Ba/td> <td align="center">53.20 (25.85 - -96.00)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">没有<gydF4y2Ba/td> <td align="center">93 (91.2)<gydF4y2Ba/td> <td align="center">21.20 (16.65 - -39.84)<gydF4y2Ba/td> <td align="center">0.04<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left"> <italic> 乙型肝炎病毒感染<gydF4y2Ba/italic></td> <td></td> <td></td> <td></td> </tr> <tr> <td align="left">乙肝病毒+<gydF4y2Ba/td> <td align="center">76 (74.5)<gydF4y2Ba/td> <td align="center">21.00 (16.49 - -44.40)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">乙肝病毒,<gydF4y2Ba/td> <td align="center">26日(25.5)<gydF4y2Ba/td> <td align="center">32.70 (18.18 - -48.60)<gydF4y2Ba/td> <td align="center">0.36<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> </tbody> </table> <table-wrap-foot> <fn> <p>注意:差:四分位范围。<gydF4y2Basup>一个<gydF4y2Ba/sup>对比分析了两组使用Mann-Whitney测试;<gydF4y2Basup>b<gydF4y2Ba/sup>比较分析了多个组中利用克鲁斯卡尔-沃利斯检验。<gydF4y2Ba/p> </fn> </table-wrap-foot> </table-wrap> </sec> <sec id="sec3.2"> <title>3.2。ssDNA水平<gydF4y2Ba/title> <p>如数据所示<gydF4y2Baxref rid="fig1" ref-type="fig"> 1<gydF4y2Ba/xref>和<gydF4y2Baxref rid="fig2" ref-type="fig"> 2<gydF4y2Ba/xref>ssDNA更高的水平在肝细胞癌(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M27"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>(所有)相对于其他疾病<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M28"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,除了胰腺癌<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M29"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。在三个肝脏疾病,肝癌是高于肝硬化(ssDNA水平<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M30"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 21<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)和慢性肝炎(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M31"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M32"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。没有健康对照组(ssDNA水平差异<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M33"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 45<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)和肝硬化患者(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M34"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M35"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.15<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)或慢性肝病(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M36"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.39<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)(表<gydF4y2Baxref rid="tab2" ref-type="table"> 2<gydF4y2Ba/xref>)。<gydF4y2Ba/p> <fig id="fig1"> <label>图1<gydF4y2Ba/label> <p>单链DNA的比较(ssDNA)水平与肝细胞癌(HCC)患者中,慢性肝脏疾病,非条件,健康的人。(中位数)的值从低到高排序。<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M37"> <mml:msup> <mml:mrow></mml:mrow> <mml:mrow> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:mrow> </mml:msup> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.05<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>与肝细胞癌;<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M38"> <mml:msup> <mml:mrow></mml:mrow> <mml:mrow> <mml:mo> ∗<gydF4y2Ba/mml:mo> <mml:mrow> <mml:mo> ∗<gydF4y2Ba/mml:mo> </mml:mrow> </mml:mrow> </mml:msup> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>与肝细胞癌。<gydF4y2Ba/p> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.001"></graphic> </fig> <fig id="fig2"> <label>图2<gydF4y2Ba/label> <p>比较积极的单链DNA (ssDNA)水平与肝细胞癌(HCC)患者中,慢性肝脏疾病,非条件,健康的人。(中位数)的值从低到高排序。<gydF4y2Ba/p> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.002"></graphic> </fig> <table-wrap id="tab2"> <label>表2<gydF4y2Ba/label> <p>比较ssDNA水平不同肝脏疾病和健康的人。<gydF4y2Ba/p> <table> <thead> <tr> <th align="left">主题<gydF4y2Ba/th> <th align="center">不。<gydF4y2Ba/th> <th align="center">ssDNA (ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L),中等(差)<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M39"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula></th> </tr> </thead> <tbody> <tr> <td align="left">健康的人<gydF4y2Ba/td> <td align="center">45<gydF4y2Ba/td> <td align="center">9.36 (8.01 - -10.90)<gydF4y2Ba/td> <td></td> </tr> <tr> <td align="left">肝硬化<gydF4y2Ba/td> <td align="center">21<gydF4y2Ba/td> <td align="center">9.64 (8.93 - -11.68)<gydF4y2Ba/td> <td align="center">0.15<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left">慢性肝炎<gydF4y2Ba/td> <td align="center">20.<gydF4y2Ba/td> <td align="center">9.76 (8.52 - -11.28)<gydF4y2Ba/td> <td align="center">0.39<gydF4y2Basup>一个<gydF4y2Ba/sup></td> </tr> <tr> <td align="left">肝细胞癌<gydF4y2Ba/td> <td align="center">102年<gydF4y2Ba/td> <td align="center">23.20 (16.86 - -44.40)<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Basup>b<gydF4y2Ba/sup></td> </tr> </tbody> </table> <table-wrap-foot> <fn> <p>差:四分位范围。<gydF4y2Basup>一个<gydF4y2Ba/sup>与健康人进行了分析使用Mann-Whitney测试;<gydF4y2Basup>b<gydF4y2Ba/sup>比较分析了多个组中利用克鲁斯卡尔-沃利斯检验。<gydF4y2Ba/p> </fn> </table-wrap-foot> </table-wrap> </sec> <sec id="sec3.3"> <title>3.3。ssDNA水平在肝细胞癌患者<gydF4y2Ba/title> <p>在肝细胞癌患者中,没有不同年龄(ssDNA水平的差异<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M40"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.99<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)、性别(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M41"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.42<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>),AFP-negative /积极的肝细胞癌(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M42"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.33<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)、肝硬化和肝细胞癌(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M43"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.64<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>子组(表)<gydF4y2Baxref rid="tab1" ref-type="table"> 1<gydF4y2Ba/xref>)。不可切除的肝细胞癌的ssDNA水平高于可切除的肝细胞癌(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M44"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.02<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。没有肿瘤大小的子组ssDNA水平的差异(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M45"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.13<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>),没有ssDNA水平与肝癌之间的相关性大小(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M46"> <mml:mi> r<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.17<gydF4y2Ba/mml:mn> <mml:mo> ,<gydF4y2Ba/mml:mo> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.10<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)(补充图<gydF4y2Baxref ref-type="supplementary-material" rid="supplementary-material-1"> S1A<gydF4y2Ba/xref>)。ssDNA水平有显著差异在不同患者TNM阶段(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M47"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.02<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)(表<gydF4y2Baxref rid="tab1" ref-type="table"> 1<gydF4y2Ba/xref>)。有一个等级和TNM分期(ssDNA水平之间的相关性<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M48"> <mml:mtext> ρ<gydF4y2Ba/mml:mtext> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.274<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>,95%置信区间CI: 0.084 - -0.444,<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M49"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 0.005<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。<gydF4y2Ba/p> </sec> <sec id="sec3.4"> <title>3.4。ssDNA HCC的诊断价值<gydF4y2Ba/title> <p>表<gydF4y2Baxref rid="tab3" ref-type="table"> 3<gydF4y2Ba/xref>和图<gydF4y2Baxref rid="fig3a" ref-type="fig"> 3(一个)<gydF4y2Ba/xref>目前的诊断价值ssDNA肝癌患者(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M50"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)和non-HCC科目(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M51"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 370年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。肝癌的AUC ssDNA独自为0.909(95%置信区间:0.879—-0.933),敏感性95.1%,特异性76.5%(表<gydF4y2Baxref rid="tab3" ref-type="table"> 3<gydF4y2Ba/xref>)。诊断效率和积极的ssDNA肝癌之间水平相似<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M52"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng / mL和<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M53"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng / mL和cirrhosis-negative和cirrhosis-positive HCC(补充表之间的关系<gydF4y2Baxref ref-type="supplementary-material" rid="supplementary-material-1"> S1<gydF4y2Ba/xref>和补充图<gydF4y2Baxref ref-type="supplementary-material" rid="supplementary-material-1"> S2<gydF4y2Ba/xref>)。所有的组合与其他着没有显著改善ssDNA ssDNA单独对肝癌的诊断价值(表<gydF4y2Baxref rid="tab3" ref-type="table"> 3<gydF4y2Ba/xref>和图<gydF4y2Baxref rid="fig3b" ref-type="fig"> 3 (b)<gydF4y2Ba/xref>)。<gydF4y2Ba/p> <table-wrap id="tab3"> <label>表3<gydF4y2Ba/label> <p>对肝癌诊断效率的各种变量。<gydF4y2Ba/p> <table> <thead> <tr> <th align="left">变量<gydF4y2Ba/th> <th align="center">最优截止值<gydF4y2Ba/th> <th align="center">森%<gydF4y2Ba/th> <th align="center">SPE %<gydF4y2Ba/th> <th align="center">AUC<gydF4y2Ba/th> <th align="center">95%可信区间<gydF4y2Ba/th> <th align="center"> <inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M54"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula></th> </tr> </thead> <tbody> <tr> <td align="left">法新社(ng / mL)<gydF4y2Ba/td> <td align="center">> 4.95<gydF4y2Ba/td> <td align="center">56.86<gydF4y2Ba/td> <td align="center">89.19<gydF4y2Ba/td> <td align="center">0.733<gydF4y2Ba/td> <td align="center">0.691 - -0.772<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CA19-9 (U /毫升)<gydF4y2Ba/td> <td align="center">> 38.8<gydF4y2Ba/td> <td align="center">50.98<gydF4y2Ba/td> <td align="center">84.05<gydF4y2Ba/td> <td align="center">0.700<gydF4y2Ba/td> <td align="center">0.656 - -0.741<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CA12-5 (U /毫升)<gydF4y2Ba/td> <td align="center">> 10.4<gydF4y2Ba/td> <td align="center">90.20<gydF4y2Ba/td> <td align="center">46.22<gydF4y2Ba/td> <td align="center">0.742<gydF4y2Ba/td> <td align="center">0.700 - -0.781<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CEA (ng / mL)<gydF4y2Ba/td> <td align="center">> 2.57<gydF4y2Ba/td> <td align="center">66.67<gydF4y2Ba/td> <td align="center">54.59<gydF4y2Ba/td> <td align="center">0.595<gydF4y2Ba/td> <td align="center">0.549 - -0.640<gydF4y2Ba/td> <td align="center">0.002<gydF4y2Ba/td> </tr> <tr> <td align="left">法新社+ CA19-9 + CA12-5 + CEA<gydF4y2Ba/td> <td align="center">> 0.1763<gydF4y2Ba/td> <td align="center">62.75<gydF4y2Ba/td> <td align="center">84.05<gydF4y2Ba/td> <td align="center">0.772<gydF4y2Ba/td> <td align="center">0.732 - -0.809<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA (ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L)<gydF4y2Ba/td> <td align="center">> 12.36<gydF4y2Ba/td> <td align="center">95.10<gydF4y2Ba/td> <td align="center">76.49<gydF4y2Ba/td> <td align="center">0.909<gydF4y2Ba/td> <td align="center">0.879 - -0.933<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">法新社+ CA199<gydF4y2Ba/td> <td align="center">> 0.1824<gydF4y2Ba/td> <td align="center">64.08<gydF4y2Ba/td> <td align="center">84.28<gydF4y2Ba/td> <td align="center">0.771<gydF4y2Ba/td> <td align="center">0.730 - -0.808<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">法新社+ CA125<gydF4y2Ba/td> <td align="center">> 0.1891<gydF4y2Ba/td> <td align="center">66.99<gydF4y2Ba/td> <td align="center">74.53<gydF4y2Ba/td> <td align="center">0.771<gydF4y2Ba/td> <td align="center">0.730 - -0.808<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">法新社+ CEA<gydF4y2Ba/td> <td align="center">> 0.2010<gydF4y2Ba/td> <td align="center">54.37<gydF4y2Ba/td> <td align="center">81.30<gydF4y2Ba/td> <td align="center">0.710<gydF4y2Ba/td> <td align="center">0.667 - -0.751<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CA199 + CA125<gydF4y2Ba/td> <td align="center">> 0<gydF4y2Ba/td> <td align="center">0.00<gydF4y2Ba/td> <td align="center">100.00<gydF4y2Ba/td> <td align="center">0.500<gydF4y2Ba/td> <td align="center">0.454 - -0.546<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CA199 + CEA<gydF4y2Ba/td> <td align="center">> 0.19279<gydF4y2Ba/td> <td align="center">71.84<gydF4y2Ba/td> <td align="center">61.52<gydF4y2Ba/td> <td align="center">0.705<gydF4y2Ba/td> <td align="center">0.662 - -0.746<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CA125 + CEA<gydF4y2Ba/td> <td align="center">> 0.20725<gydF4y2Ba/td> <td align="center">47.57<gydF4y2Ba/td> <td align="center">88.89<gydF4y2Ba/td> <td align="center">0.736<gydF4y2Ba/td> <td align="center">0.694 - -0.775<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">法新社+ CA199 + CEA<gydF4y2Ba/td> <td align="center">> 0.185<gydF4y2Ba/td> <td align="center">60.19<gydF4y2Ba/td> <td align="center">86.99<gydF4y2Ba/td> <td align="center">0.777<gydF4y2Ba/td> <td align="center">0.736 - -0.813<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">法新社+ CA199 + CA125<gydF4y2Ba/td> <td align="center">> 0.17613<gydF4y2Ba/td> <td align="center">66.02<gydF4y2Ba/td> <td align="center">82.11<gydF4y2Ba/td> <td align="center">0.783<gydF4y2Ba/td> <td align="center">0.743 - -0.819<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">CA199 + CA125 + CEA<gydF4y2Ba/td> <td align="center">> 0.18432<gydF4y2Ba/td> <td align="center">59.22<gydF4y2Ba/td> <td align="center">82.38<gydF4y2Ba/td> <td align="center">0.751<gydF4y2Ba/td> <td align="center">0.710 - -0.790<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社+ CA199<gydF4y2Ba/td> <td align="center">> 0.16065<gydF4y2Ba/td> <td align="center">87.38<gydF4y2Ba/td> <td align="center">81.30<gydF4y2Ba/td> <td align="center">0.902<gydF4y2Ba/td> <td align="center">0.872 - -0.927<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社+ CA125<gydF4y2Ba/td> <td align="center">> 0.1669<gydF4y2Ba/td> <td align="center">85.44<gydF4y2Ba/td> <td align="center">83.47<gydF4y2Ba/td> <td align="center">0.905<gydF4y2Ba/td> <td align="center">0.875 - -0.930<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社+ CEA<gydF4y2Ba/td> <td align="center">> 0.15144<gydF4y2Ba/td> <td align="center">93.20<gydF4y2Ba/td> <td align="center">78.05<gydF4y2Ba/td> <td align="center">0.907<gydF4y2Ba/td> <td align="center">0.877 - -0.932<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CA199 + CA125<gydF4y2Ba/td> <td align="center">> 0.16608<gydF4y2Ba/td> <td align="center">84.47<gydF4y2Ba/td> <td align="center">82.66<gydF4y2Ba/td> <td align="center">0.900<gydF4y2Ba/td> <td align="center">0.869 - -0.925<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CA199 + CEA<gydF4y2Ba/td> <td align="center">> 0.17043<gydF4y2Ba/td> <td align="center">85.44<gydF4y2Ba/td> <td align="center">83.47<gydF4y2Ba/td> <td align="center">0.900<gydF4y2Ba/td> <td align="center">0.869 - -0.925<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CA125 + CEA<gydF4y2Ba/td> <td align="center">> 0.17867<gydF4y2Ba/td> <td align="center">83.50<gydF4y2Ba/td> <td align="center">85.91<gydF4y2Ba/td> <td align="center">0.905<gydF4y2Ba/td> <td align="center">0.875 - -0.930<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社+ CA199 + CA125<gydF4y2Ba/td> <td align="center">> 0.15393<gydF4y2Ba/td> <td align="center">89.32<gydF4y2Ba/td> <td align="center">78.86<gydF4y2Ba/td> <td align="center">0.902<gydF4y2Ba/td> <td align="center">0.872 - -0.927<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社+ CA199 + CEA<gydF4y2Ba/td> <td align="center">> 0.16522<gydF4y2Ba/td> <td align="center">86.41<gydF4y2Ba/td> <td align="center">83.47<gydF4y2Ba/td> <td align="center">0.901<gydF4y2Ba/td> <td align="center">0.871 - -0.927<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CA199 + CA125 + CEA<gydF4y2Ba/td> <td align="center">> 0.16153<gydF4y2Ba/td> <td align="center">87.38<gydF4y2Ba/td> <td align="center">81.57<gydF4y2Ba/td> <td align="center">0.901<gydF4y2Ba/td> <td align="center">0.870 - -0.926<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社<gydF4y2Ba/td> <td align="center">> 0.1448<gydF4y2Ba/td> <td align="center">95.10<gydF4y2Ba/td> <td align="center">76.49<gydF4y2Ba/td> <td align="center">0.911<gydF4y2Ba/td> <td align="center">0.882 - -0.935<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CA19-9<gydF4y2Ba/td> <td align="center">> 0.1433<gydF4y2Ba/td> <td align="center">95.10<gydF4y2Ba/td> <td align="center">74.59<gydF4y2Ba/td> <td align="center">0.904<gydF4y2Ba/td> <td align="center">0.874 - -0.929<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CA12-5<gydF4y2Ba/td> <td align="center">> 0.1533<gydF4y2Ba/td> <td align="center">90.20<gydF4y2Ba/td> <td align="center">78.65<gydF4y2Ba/td> <td align="center">0.906<gydF4y2Ba/td> <td align="center">0.876 - -0.931<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA + CEA<gydF4y2Ba/td> <td align="center">> 0.1529<gydF4y2Ba/td> <td align="center">94.12<gydF4y2Ba/td> <td align="center">78.38<gydF4y2Ba/td> <td align="center">0.909<gydF4y2Ba/td> <td align="center">0.880 - -0.934<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> <tr> <td align="left">ssDNA +法新社+ CA19-9 + CA12-5 + CEA<gydF4y2Ba/td> <td align="center">> 0.1555<gydF4y2Ba/td> <td align="center">89.22<gydF4y2Ba/td> <td align="center">81.89<gydF4y2Ba/td> <td align="center">0.905<gydF4y2Ba/td> <td align="center">0.875 - -0.930<gydF4y2Ba/td> <td align="center">< 0.001<gydF4y2Ba/td> </tr> </tbody> </table> <table-wrap-foot> <fn> <p>法新社:甲胎蛋白;CA:肿瘤抗原;东航:癌胚抗原;ssDNA:单链DNA;森:敏感性;SPE:特异性;AUC:曲线下的面积;置信区间:置信区间。<gydF4y2Ba/p> </fn> </table-wrap-foot> </table-wrap> <fig-group id="fig3"> <label>图3<gydF4y2Ba/label> <p>接受者操作特征(ROC)曲线不同的HCC诊断的标记:<gydF4y2Baitalic> α<gydF4y2Ba/italic>胎蛋白(AFP)、癌抗原(CA)波,CA12-5,癌胚抗原(CEA)和单链DNA (ssDNA)在肝细胞癌(HCC)患者:(a) ROC曲线传统的肿瘤标志物(着)(法新社,CA19-9、CA12-5和CEA)和ssDNA;(b)中华民国ssDNA结合着。<gydF4y2Ba/p> <fig id="fig3a"> <label>(一)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.003a"></graphic> </fig> <fig id="fig3b"> <label>(b)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.003b"></graphic> </fig> </fig-group> </sec> <sec id="sec3.5"> <title>3.5。着的肝细胞癌患者的诊断价值<gydF4y2Ba/title> <p>表<gydF4y2Baxref rid="tab3" ref-type="table"> 3<gydF4y2Ba/xref>介绍了诊断值着的肝癌患者(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M55"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 102年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)和non-HCC学科(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M56"> <mml:mi> n<gydF4y2Ba/mml:mi> <mml:mo> =<gydF4y2Ba/mml:mo> <mml:mn> 370年<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)。肝癌的AUC CA12-5独自为0.742(95%置信区间:0.700—-0.781),敏感性为90.2%,特异性46.2%。法新社的AUC HCC仅为0.733(95%置信区间:0.691—-0.722),敏感性为56.9%,特异性89.2%。仅CA19-9和CEA的auc肝癌都低于CA12-5和法新社。结合着的敏感性(法新社,CA19-9、CA12-5和CEA)为62.8%,特异性为84.1%,AUC为0.772(95%置信区间:0.732—-0.809)。多个组合进行测试;所有的组合,包括ssDNA auc高于不包括ssDNA组合。<gydF4y2Ba/p> </sec> <sec id="sec3.6"> <title>3.6。比较积极的ssDNA在不同疾病<gydF4y2Ba/title> <p>使用<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M57"> <mml:mtext> ssDNA<gydF4y2Ba/mml:mtext> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 12.36<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L作为最优截止值,积极的ssDNA肝癌患者(97/102)明显高于non-HCC科目(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M58"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>)(图<gydF4y2Baxref rid="fig2" ref-type="fig"> 2<gydF4y2Ba/xref>)。<gydF4y2Ba/p> </sec> <sec id="sec3.7"> <title>3.7。ssDNA水平变化和Postradical手术肝癌患者<gydF4y2Ba/title> <p>成对ssDNA结果表明,62年的ssDNA水平可切除的肝细胞癌患者在手术后3天达到顶峰,拒绝与AFP水平(补充图的衰落<gydF4y2Baxref ref-type="supplementary-material" rid="supplementary-material-1"> S3<gydF4y2Ba/xref>)。的水平ssDNA稳定手术后60天左右,和平均水平下降了3.19倍(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M59"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.001<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>与基线相比)。根据最优截止ssDNA (> 12.36 ng /的值<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L), 11 ssDNA水平可切除的肝细胞癌患者没有回到低水平(即。,< 12.36 ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L)在手术后60天内,其中的6个11对患者进行评估基于RECIST CR。<gydF4y2Ba/p> </sec> <sec id="sec3.8"> <title>3.8。ssDNA水平和疾病预后之间的关系<gydF4y2Ba/title> <p>ssDNA水平的长期随访上述六个CR患者进行识别的预后价值ssDNA HCC(补充表<gydF4y2Baxref ref-type="supplementary-material" rid="supplementary-material-1"> S2<gydF4y2Ba/xref>)。根据1.1 RECIST疾病反应进行评估。线图表的绘制在后续描述ssDNA水平变化。如图<gydF4y2Baxref rid="fig4" ref-type="fig"> 4<gydF4y2Ba/xref>,ssDNA水平的六名病人增加6 - 12个月的随访中,但在疾病进展由RECIST决定。<gydF4y2Ba/p> <fig-group id="fig4"> <label>图4<gydF4y2Ba/label> <p>行单链DNA的图表(ssDNA)水平在串行跨度为肝细胞癌(HCC)患者取得了完全缓解(CR)激进手术后随访期间复发和确认。SD:稳定的疾病;帕金森病:进步的疾病。<gydF4y2Baitalic> α<gydF4y2Ba/italic>胎蛋白-(法新社)积极的HCC患者被定义为<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M60"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> ><gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng / mL。<gydF4y2Ba/p> <fig id="fig4a"> <label>(一)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.004a"></graphic> </fig> <fig id="fig4b"> <label>(b)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.004b"></graphic> </fig> <fig id="fig4c"> <label>(c)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.004c"></graphic> </fig> <fig id="fig4d"> <label>(d)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.004d"></graphic> </fig> <fig id="fig4e"> <label>(e)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.004e"></graphic> </fig> <fig id="fig4f"> <label>(f)<gydF4y2Ba/label> <graphic xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.fig.004f"></graphic> </fig> </fig-group> </sec> <sec id="sec3.9"> <title>3.9。ssDNA差异和dsDNA水平根据提取方法<gydF4y2Ba/title> <p>补充图<gydF4y2Baxref ref-type="supplementary-material" rid="supplementary-material-1"> S4<gydF4y2Ba/xref>表明,磁珠方法产生一个更好的提取效率比QIAmp循环核酸工具包(Venlo试剂盒,荷兰)(<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M61"> <mml:mi> P<gydF4y2Ba/mml:mi> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 0.01<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>),而没有差异dsDNA之间的两个方法。此外,auc ssDNA和dsDNA HCC的诊断分别为0.909和0.880,分别有95.1%和88.2%的敏感性和特异性76.5%和79.7%。<gydF4y2Ba/p> </sec> </sec> <sec id="sec4"> <title>4所示。讨论<gydF4y2Ba/title> <p>有一个缺乏可靠的生物标志物对于肝细胞癌(<gydF4y2Baxref ref-type="bibr" rid="B7"> 7<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B9"> 9<gydF4y2Ba/xref>]。高血浆水平ssDNA基因组不稳定性的一个标志。本探索性研究旨在探索的价值ssDNA HCC诊断和预后的标志通过分析102例肝细胞癌患者和370名对照。结果表明ssDNA可能是一种无创性指标肝癌诊断和预后和可能补充法新社和成像,但研究还需要确认和验证结果。不过,结果表明ssDNA可以用来筛选肝癌患者怀疑肝癌但消极法新社和不确定的成像。<gydF4y2Ba/p> <p>使用cfDNA肿瘤诊断、治疗和预后是有前途的<gydF4y2Baxref ref-type="bibr" rid="B16"> 16<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B20"> 20.<gydF4y2Ba/xref>]。cfDNA收益率高的磁珠提取效率和质量(<gydF4y2Baxref ref-type="bibr" rid="B19"> 19<gydF4y2Ba/xref>- - - - - -<gydF4y2Baxref ref-type="bibr" rid="B27"> 27<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B32"> 32<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B33"> 33<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B35"> 35<gydF4y2Ba/xref>]。因此,在这项研究中,磁珠被用来提取cfDNA。量子位ssDNA分析工具包ssDNA不是特定的,它还将检测dsDNA和RNA。因此,进行方法学评价验证cfDNA的提取方法。结果表明ssDNA提取效率使用磁珠可以约两倍的QIAmp循环核酸工具包(Venlo试剂盒,荷兰)和DNA提取的核酸被证实。自从cfDNA ssDNA水平远高于dsDNA [<gydF4y2Baxref ref-type="bibr" rid="B23"> 23<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B24"> 24<gydF4y2Ba/xref>),dsDNA的干扰ssDNA决心可能不会影响的结论,但这将会验证在一个特定的方法论的研究。<gydF4y2Ba/p> <p>cfDNA显著增加的血液水平当病人患有肿瘤、自身免疫性疾病、传染性疾病,中风和心肌梗死<gydF4y2Baxref ref-type="bibr" rid="B36"> 36<gydF4y2Ba/xref>]。为了排除这些疾病的影响ssDNA水平对肝癌的诊断价值,健康的个人和肝硬化患者,慢性肝炎,代谢疾病、循环系统疾病、自身免疫性疾病和各种肿瘤除了肝癌被用作各种对照组。结果表明,肝细胞癌患者ssDNA水平明显高于其他所有疾病,和ROC曲线的AUC 0.909 HCC诊断。因此,ssDNA似乎是一个特定肝癌而不干扰其他疾病的生物标志物。与法新社和着相比,ssDNA可能提高肝癌诊断。ssDNA的组合与任何着没有有效地提高诊断价值,表明ssDNA可能起到至关重要的诊断为肝癌的诊断作用,所支持的一项研究[<gydF4y2Baxref ref-type="bibr" rid="B37"> 37<gydF4y2Ba/xref>]。此外,HCC ssDNA水平是高于慢性疾病与肝细胞癌的风险更高(肝硬化和慢性肝炎)<gydF4y2Baxref ref-type="bibr" rid="B7"> 7<gydF4y2Ba/xref>]。另一方面,没有差异,在肝细胞癌患者的诊断价值和没有肝硬化或有与没有肝炎,表明ssDNA是特定于肝细胞癌,从伴随肝条件没有干扰。虽然复制压力是重要但可控的慢性肝炎、肝硬化和肝细胞癌具有较高的复制的压力。这些结果表明,ssDNA有很好的鉴别诊断对肝癌的影响,它可能是独立于肝硬化和肝炎。间接支持目前的研究中,金等。<gydF4y2Baxref ref-type="bibr" rid="B38"> 38<gydF4y2Ba/xref>)表明,ssDNA-binding蛋白2的表达升高患者积极的肝癌。杜et al。<gydF4y2Baxref ref-type="bibr" rid="B39"> 39<gydF4y2Ba/xref>和盾等。<gydF4y2Baxref ref-type="bibr" rid="B40"> 40<gydF4y2Ba/xref>]表明,特定于ssDNA寡核苷酸适配子可以识别肝癌。然而,ssDNA截止值必须决定使用大规模的多中心研究。的确,在本研究最优截止ssDNA价值> 12.36 ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L,而陈等人报道的最优值> 509.98 ng / mL [<gydF4y2Baxref ref-type="bibr" rid="B41"> 41<gydF4y2Ba/xref>]。<gydF4y2Ba/p> <p>同样有趣的是,至于cirrhosis-associated HCC, ssDNA水平没有差异,ssDNA诊断效率,ssDNA肝癌之间积极的利率<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M62"> <mml:mtext> 法新社<gydF4y2Ba/mml:mtext> <mml:mo> <<gydF4y2Ba/mml:mo> <mml:mn> 20.<gydF4y2Ba/mml:mn> </mml:math> </inline-formula>ng / mL和> 20 ng / mL。这些结果暗示ssDNA水平可能与法新社表达和ssDNA可以弥补缺乏的法新社AFP-negative HCC的诊断。<gydF4y2Ba/p> <p>ssDNA可能使用病人的随访。这项研究表明,与AFP水平不同,ssDNA水平达到峰值后开始下降3天后手术,这可能反映了循环肿瘤切除后DNA快速释放<gydF4y2Baxref ref-type="bibr" rid="B42"> 42<gydF4y2Ba/xref>]。众所周知,术后AFP水平的下降通常反映了肝细胞癌治疗的有效性(<gydF4y2Baxref ref-type="bibr" rid="B43"> 43<gydF4y2Ba/xref>,<gydF4y2Baxref ref-type="bibr" rid="B44"> 44<gydF4y2Ba/xref>]。在目前的研究中,ssDNA水平稳定在手术后60天。在分析六个患者完全缓解,其ssDNA水平并未回到低水平(即。,< 12.36 ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L)手术后,ssDNA达到6 - 12个月的随访,后来跟着一个确认肝癌复发的成像。这些结果表明,ssDNA可以用来显示肝细胞癌根治切除术的有效性和HCC预后在法新社和成像。它是由金等。<gydF4y2Baxref ref-type="bibr" rid="B38"> 38<gydF4y2Ba/xref>),表明ssDNA-binding蛋白2的水平与生存相关肝细胞癌。更多的研究是必要的来证实这些结果。<gydF4y2Ba/p> <p>本研究有几个局限性。首先,由于没有数据可以从文献研究执行时,病人的便利样本符合资格的标准在研究期间必须使用。第二,截止值的阈值是基于ROC分析,需要在一个独立的验证队列进行验证。第三,考虑到中等数量的肝癌患者纳入本研究,结论要谨慎对待,特别是在边缘的存在<gydF4y2Bainline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M63"> <mml:mi> P<gydF4y2Ba/mml:mi> </mml:math> </inline-formula>值。这是一个探索性的分析,研究对象为中华民国分析只是分组HCC和non-HCC。正式的比较在不同类型的癌症及其特征将是未来研究的重点。第四,由于少数患者随访,ssDNA在HCC进展和预后的应用需要进一步探索。第五,ssDNA之间的关系和其他的功效HCC-related治疗没有被评估。最后,不可切除的肝细胞癌患者的ssDNA水平高于可切除的肝细胞癌患者,但目前的研究没有探讨ssDNA是否可以用来确定resectability。这些问题还需要进一步研究。<gydF4y2Ba/p> </sec> <sec id="sec5"> <title>5。结论<gydF4y2Ba/title> <p>这项研究表明ssDNA可能是一种无创性肝细胞癌诊断和预后指标。确认结果是必要和HCC的ssDNA截止值的确定诊断。<gydF4y2Ba/p> </sec> <back> <sec sec-type="data-availability"> <title>数据可用性<gydF4y2Ba/title> <p>和/或使用的数据集和数据分析了在目前的研究可从相应的作者以合理的要求。<gydF4y2Ba/p> </sec> <sec> <title>伦理批准<gydF4y2Ba/title> <p>伦理委员会批准的研究协议的附属无锡第二人民医院南京医科大学。<gydF4y2Ba/p> </sec> <sec> <title>同意<gydF4y2Ba/title> <p>所有参与者提供书面知情同意。<gydF4y2Ba/p> </sec> <sec sec-type="COI-statement"> <title>的利益冲突<gydF4y2Ba/title> <p>作者宣称没有利益冲突有关的出版。<gydF4y2Ba/p> </sec> <sec> <title>作者的贡献<gydF4y2Ba/title> <p>Xuewen黄执行概念和设计;发展的方法、分析和解释;和写作,评论,和/或修改的手稿。齐赵采集的数据,进行分析和解释。Yiqiu徐采集的数据,进行分析和解释。丹丹元进行分析和解释和评论和/或修改的手稿。军军杨收购数据和分析和解释执行。应王,国荣沈执行方法的发展。赵七,Yiqiu徐,丹丹元,军军,应王,国荣沈了同样的工作。<gydF4y2Ba/p> </sec> <ack> <title>确认<gydF4y2Ba/title> <p>我们要感谢黄Junyu清华大学数学系的学生,统计支持本研究。我们还要感谢所有成员提供他们的专业知识和帮助临床前研究。<gydF4y2Ba/p> </ack> <sec sec-type="supplementary-material" id="supplementary-material-1"> <title>补充材料<gydF4y2Ba/title> <supplementary-material xlink:href="//www.newsama.com/downloads/journals/dm/2021/9958909.f1.docx" id="supp-1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document"> <label>补充材料<gydF4y2Ba/label> <p>补充表S1: ssDNA HCC诊断效率。补充表S2。标记的特点六患者完全缓解,随访。补充图S1。ssDNA水平和肿瘤大小之间的关系(肿瘤最大直径之和)。(一)线性ssDNA水平和肿瘤大小之间的关系。方程是y = 32.744 + 0.405 x, r = 0.17, P = 0.095。在补充图1箭头指向的病例。(B) Case1(肿瘤大小:11毫米;ssDNA水平:48.6 ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L;AFP水平:267 ng / mL)。(C)例2(肿瘤大小:84毫米;ssDNA水平:453 ng / mL;AFP水平:1.63 ng / mL) (D) Case3(肿瘤大小:172毫米,ssDNA水平:23.8 ng /<gydF4y2Baitalic> μ<gydF4y2Ba/italic>L, AFP水平:520 ng / mL)。补充图1中的箭头罪犯病变。补充图S2。比较积极的ssDNA AFP-negative HCC和AFP-positive HCC之间Cirrhosis-negative HCC和Cirrhosis-positive肝癌。补充图S3。ssDNA和AFP水平的变化和术后肝癌。(一)ssDNA。(B)。* *<gydF4y2Baitalic> P<gydF4y2Ba/italic>< 0.01。补充图S4。确认cfDNA磁珠方法的提取效率和cfDNA自然。(A)之间的ssDNA提取效率比较的方法。(B)之间的dsDNA提取效率比较的方法。(C)安捷伦2100化验结果cfDNA提取前消化。(d e)安捷伦2100化验结果cfDNA提取核糖核酸酶消化和DNase我消化后,分别。NS:<gydF4y2Baitalic> P<gydF4y2Ba/italic>> 0.05。* *<gydF4y2Baitalic> P<gydF4y2Ba/italic>< 0.01。<gydF4y2Ba/p> </supplementary-material> </sec> <ref-list> <ref id="B1" content-type="article"> <label>1<gydF4y2Ba/label> <element-citation publication-type="journal"> <person-group person-group-type="author"> <name> <surname> 布雷<gydF4y2Ba/surname> <given-names> F。<gydF4y2Ba/given-names> </name> <name> <surname> Ferlay<gydF4y2Ba/surname> <given-names> J。<gydF4y2Ba/given-names> </name> <name> <surname> Soerjomataram<gydF4y2Ba/surname> <given-names> 我。<gydF4y2Ba/given-names> </name> <name> <surname> 西格尔<gydF4y2Ba/surname> <given-names> r . 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