摘要
目的检测原发性肝细胞癌(hepatocellular carcinoma,HCC)血浆中环状RNA(circular RNA,circRNA)hsa_circ_0003998表达水平,探讨其在HCC诊断和预后评估的临床价值。方法通过转录组测序(RNA-sequening,RNA-seq)检测6例HCC癌组织(有/无门静脉侵犯者各3例)的circRNA表达情况。采用实时荧光定量反转录聚合酶链反应(Quantitative reverse transcription-polymerase chain reaction,qRT-PCR)检测80例HCC、20例乙型肝炎和20例健康人血浆中hsa_circ_0003998表达水平,并分析其与HCC患者临床病理特征的关系。应用受试者工作特征曲线(Receiver operator characteristic curve,ROC)评估hsa_circ_0003998诊断HCC的临床价值。应用Kaplan-Meier法进行生存分析,log-rank法进行预后单因素分析,COX回归进行预后多因素分析。结果发现有门静脉侵犯的HCC癌组织中hsa_circ_0003998表达水平显著高于无门静脉侵犯者。HCC血浆中hsa_circ_0003998表达水平显著高于乙型肝炎组和健康人组,差异有统计学意义(3.12±1.97vs 1.43±0.91,P<0.001;3.12±1.97vs 1.21±1.08,P<0.001),且其高表达水平与HCC的血清甲胎蛋白(alpha-fetoprotien,AFP)(P=0.012)、肿瘤直径(P=0.007)、TNM分期(P=0.011)及组织分化程度(P=0.015)显著相关。ROC曲线分析显示,血浆hsa_circ_0003998在鉴别HCC与健康人、乙型肝炎的曲线下面积(Area under of ROC curve,AUC)分别为0.848和0.807。hsa_circ_0003998低表达组的总生存时间(overall survival,OS)显著长于高表达组(34.91±1.75vs 27.26±1.82,P=0.002)。预后单因素分析显示,AFP(P=0.004)、TNM分期(P=0.013)和hsa_circ_0003998表达水平(P=0.003)与HCC的OS显著相关。预后多因素分析显示,hsa_circ_0003998表达水平(P=0.041)和AFP(P=0.039)是HCC的独立预后因素。结论 hsa_circ_0003998可能作为一种新型的生物学标志物应用于HCC的诊断和预后评估。
Objective Detecting plasma level of circular RNA(circRNA)hsacirc0003998 in primary hepatocellular carcinoma(HCC)patients,and investigate the clinical value of hsacirc0003998 in diagnosis and prognostic evaluation of HCC.Methods The global circRNA expression was measured by RNA-sequening(RNA-seq)in six cases of HCC tissues(three cases with or without portal vein invasion).We examined plasma hsacirc0003998 levels in 80 HCC samples,20 hepatitis B plasma samples and 20 healthy volunteer samples by quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and analyzed its clinicopathologic significance.The clinical value of hsacirc0003998 in diagnosis of HCC was analyzed by receiver operating characteristic(ROC)curve.The survival analysis was conducted by Kaplan-Meier curve,and the univariate analysis of prognostic factors was performed by log-rank test.The multivariate analysis was conducted by COX analysis.Results The expression level of hsacirc0003998 in HCC tissues with portal vein invasion was significantly higher than those without portal vein invasion.Plasma level of hsacirc0003998 in HCC was significantly higher than hepatitis B patients and healthy volunteers(3.12±1.97 vs 1.43±0.91,P<0.001;3.12±1.97 vs 1.21±1.08,P<0.001).In addition,the high level of hsacirc0003998 was associated with serum AFP level(P=0.012),tumor diameter(P=0.007),TNM staging(P=0.0011)and histological differentiation(P=0.015).The area under the ROC curve(AUC)of plasma hsacirc0003998 in discriminating the patients with HCC from healthy volunteers and hepatitis B patients was 0.848 and 0.807 respectively.The overall survival of HCC patients with low hsacirc0003998 expression was significantly better than those with high expression(34.91±1.75 vs 27.26±1.82,P=0.002).The results of univariate analysis showed that serum AFP level(P=0.004),TNM staging(P=0.013)and plasma level of hsacirc0003998(P=0.003)were significantly associated with OS of HCC.Multivariate analysis revealed that hsacirc0003998(P=0.041)and AFP level(P=0.039)were
作者
杨春梅
乔光磊
宋丽娜
吴伟琪
陈颖
夏薇
马俐君
YANG Chun-mei;QIAO Guang-lei;SONG Li-na(Beihua University,Jilin132013,China;Department of Oncology,Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200336,China)
出处
《中国实验诊断学》
2019年第5期761-766,共6页
Chinese Journal of Laboratory Diagnosis
基金
国家自然科学基金(81672335)
上海市卫生和计划生育委员会科研课题(201640275
201740055
20174Y0231)
