高表达miR-3682-3p是肝细胞癌患者的不良预后因素

High expression ofmiR-3682-3p is an unfavorable prognostic factor of hepatocellular carcinoma

目的分析miR-3682-3p在HCC中的表达及其与临床参数和预后的相关性。方法生物信息学分析miR-3682-3p在HCC中的表达以及与生存相关性;实时荧光定量PCR和原位杂交分别检测miR-3682-3p(miR-3682)在18对HCC与癌旁新鲜肝组织以及90对石蜡包埋HCC及其癌旁组织中的表达差异。统计分析miR-3682-3p在HCC中的表达与患者临床参数和预后之间的关系。利用多因素回归分析探讨miR-3682-3p表达作为肝细胞癌预后独立因素的可能性。结果生物信息分析显示,miR-3682-3p在HCC组织中高表达,且与HCC患者综合生存时间有统计学关联(χ^(2)=8.793,P<0.001)。实时荧光定量PCR分析18组配对的HCC和癌旁肝组织显示,miR-3682-3p在癌组织中表达明显上调(t=3.073,P=0.007)。原位杂交分析90组配对的HCC和癌旁组织中miR-3682-3p的表达,显示其在癌与癌旁组织的细胞浆中表达,并且在癌组织中表达上调(t=2.659,P=0.009)。miR-3682-3p表达的高低在美国癌症联合委员会(AJCC)第八版分期(χ^(2)=4.272,P=0.039)、HBV表面抗原状态(χ^(2)=5.143,P=0.023)、复发(χ^(2)=4.593,P=0.032)、肿瘤大小(χ^(2)=4.580,P=0.032)和Edmondson-Steiner分级(χ^(2)=4.068,P=0.044)方面差异存在统计学意义;Kaplan-Meier分析显示,miR-3682-3p表达越高,患者总生存时间(Log rankχ^(2)=4.169,P=0.041)和无病生存时间(Log rankχ^(2)=4.078,P=0.043)越短。多变量分析显示,miR-3682-3p表达是评估HCC患者预后独立因子。结论miR-3682-3p在HCC组织中表达上调,是促进HCC发病和预后不良的重要因子。

Objective To investigate the expression of miR-3682-3p in hepatocellular carcinoma(HCC)and its correlation with clinical parameters and prognosis of HCC.Methods We conducted a bioinformatics analysis of the expression of miR-3682-3p in HCC and its correlation with the patients'survival,and examined its expression in 18 pairs of fresh and 90 pairs of paraffin-embedded HCC and adjacent tissues using real-time fluorescence quantitative PCR and in situ hybridization,respectively.The correlation of miR-3682-3p expression in HCC with the clinical parameters and prognosis of the patients was analyzed.Multivariate regression analysis was used to explore the possibility of miR-3682-3p expression as an independent prognostic factor of HCC.Results Bioinformatics analysis showed that miR-3682-3p was highly expressed in HCC and significantly correlated with the survival time of HCC patients(χ^(2)=8.793,P<0.001).The expression of miR-3682-3p was significantly up-regulated in fresh HCC tissues as compared with the adjacent liver tissues(t=3.073,P=0.007).In paraffin-embedded samples,in situ hybridization revealed positive miR-3682-3p expression in the cytoplasm of HCC and adjacent tissues,and its expression was signifcantly up-regulated in HCC tissues(t=2.659,P=0.009).The expression level of miR-3682-3p was significantly correlated with American Joint Commission on Cancer(AJCC;8th edition)stage(χ^(2)=4.272,P=0.039),HBV surface antigen status(χ^(2)=5.143,P=0.023),recurrence(χ^(2)=4.593,P=0.032),tumor size(χ^(2)=4.580,P=0.032)and Edmondson Steiner grade(χ^(2)=4.068,P=0.044).Kaplan-Meier analysis showed that a higher expression of miR-3682-3p was associated with a shorter overall survival time(χ^(2)=4.169,P=0.041)and disease-free survival time(χ^(2)=4.078,P=0.043)of the patients.Multivariate analysis suggested that miR-3682-3p expression was an independent predictor of the prognosis of HCC patients.Conclusion MiR-3682-3p is up-regulated in HCC to serve as a significant factor that contributes to the occurrence and a poor prognosis of HCC.