STAT3基因多态性及其与HBV前C区基因突变的交互作用对肝细胞癌发病的影响
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摘要
[目的]探讨信号传导和转录激活因子3(STAT3)基因rs2293152位点单核苷酸多态性(SNPs)及其与乙型肝炎病毒(HBV)前C区G1896A基因突变的交互作用对肝细胞癌(HCC)发病的影响。[方法]采用以医院为基础11配比病例对照研究方法,选取HBV感染合并HCC患者206例作为观察组,同期HBV感染非合并HCC患者206例作为对照组,应用聚合酶链反应-限制性片段长度多态性技术检测2组STAT3基因rs2293152位点SNPs,应用分子信标荧光定量聚合酶链反应技术测定HBV前C区G1896A基因突变。采用二分类Logistic回归模型分析STAT3基因rs2293152位点SNPs与HCC遗传易感性的关系,并探究rs2293152位点SNPs与HBV前C区G1896A基因突变的交互作用对HCC发病影响。[结果]对照组与观察组间STAT3基因rs2293152位点基因型分布差异无统计学意义(P>0.05)。STAT3基因rs2293152位点G等位基因可增加HCC发病风险(P <0.05)。分层分析发现,在HBV前C区G1896A基因突变患者中rs2293152位点GG基因型相比GC+CC基因型,HCC发病风险升高,差异有统计学意义(P<0.05)。交互作用分析示,STAT3基因rs2293152位点SNPs与HBV前C区G1896A基因突变存在正交互作用。[结论]STAT3基因rs2293152位点SNPs与HCC遗传易感性明显相关,并与HBV前C区G1896A基因突变存在正交互作用,可增加HCC发病风险。
[Objective]This study aimed to investigate the effect of STAT3 gene single nucleotide polymorphisms(SNPs)and its interaction with hepatitis B virus(HBV)precore mutation on the risk of hepatocellular carcinoma(HCC).[Methods]The case-control study was a hospital-based 1:1matched study.206 patients with HBV infections and HCC were enrolled as the observational group,while 206 subjects with HBV infections were enrolled as the control group.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the SNPs of STAT3 rs2293152.Molecular beacon fluorescence quantitative polymerase chain reaction was employed to determine the G1896 Agene mutation in pre-C region of HBV.Binary logistic regression analyses were used to explore the associations between SNPs of STAT3 rs2293152 and the hereditary susceptibility of HCC,and their interactions with HBV precore mutation on the risk of HCC.[Results]No significant difference was observed in the distribution of genotypes of STAT3 rs2293152 between the control group and observational group(P>0.05).G alley of STAT3 rs2293152 could increase the risk of HCC(P<0.05).Stratified analysis found that in patients with HBV precore mutation,STAT3 rs2293152 GG genotype compared to GC+CC genotype,had the higher risk of HCC(P<0.05).Interaction assay demonstrated that STAT3 rs2293152 SNPs were positively interacted HBV precore mutation.[Conclusion]The SNPs of STAT3 rs2293152 were closely related with the hereditary susceptibility of HCC,and positively interacted with HBV precore mutation,which could increase the HCC risk.
[Objective]This study aimed to investigate the effect of STAT3 gene single nucleotide polymorphisms(SNPs)and its interaction with hepatitis B virus(HBV)precore mutation on the risk of hepatocellular carcinoma(HCC).[Methods]The case-control study was a hospital-based 1:1matched study.206 patients with HBV infections and HCC were enrolled as the observational group,while 206 subjects with HBV infections were enrolled as the control group.Polymerase chain reaction-restriction fragment length polymorphism was used to detect the SNPs of STAT3 rs2293152.Molecular beacon fluorescence quantitative polymerase chain reaction was employed to determine the G1896 Agene mutation in pre-C region of HBV.Binary logistic regression analyses were used to explore the associations between SNPs of STAT3 rs2293152 and the hereditary susceptibility of HCC,and their interactions with HBV precore mutation on the risk of HCC.[Results]No significant difference was observed in the distribution of genotypes of STAT3 rs2293152 between the control group and observational group(P>0.05).G alley of STAT3 rs2293152 could increase the risk of HCC(P<0.05).Stratified analysis found that in patients with HBV precore mutation,STAT3 rs2293152 GG genotype compared to GC+CC genotype,had the higher risk of HCC(P<0.05).Interaction assay demonstrated that STAT3 rs2293152 SNPs were positively interacted HBV precore mutation.[Conclusion]The SNPs of STAT3 rs2293152 were closely related with the hereditary susceptibility of HCC,and positively interacted with HBV precore mutation,which could increase the HCC risk.
引文
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[13]朴金梅,刘梦,李成成,等.STAT4rs7574865GG基因型与GT+TT基因型肝癌患者相关危险因素对比分析[J].中华肿瘤防治杂志,2017,24(2):84-86.
[14]Dondeti MF,El-Maadawy EA,Talaat RM.Hepatitisrelated hepatocellular carcinoma:Insights into cytokine gene polymorphisms[J].World J Gastroenterol,2016,22(30):6800-6816.
[15]Alavi M,Law MG,Grebely J,et al.Time to decompensated cirrhosis and hepatocellular carcinoma after an HBV or HCV notification:A population-based study[J].J Hepatol,2016,65(5):879-887.
[16]Levrero M,Zucman-Rossi J.Mechanisms of HBV-induced hepatocellular carcinoma[J].J Hepatol,2016,64(1Suppl):S84-S101.
[17]Liao Y,Hu X,Chen J,et al.Precore mutation of hepatitis B virus may contribute to hepatocellular carcinoma risk:evidence from an updated meta-analysis[J].PLoS One,2012,7(6):e38394.
[18]曾俊涛,陈静,曾仕平,等.黎族HBV感染者其病毒基因型及C基因启动子/前C区基因突变与肝硬化和肝癌的关系[J].中华肝脏病杂志,2011,19(12):936-938.
[19]Suppiah J,Zain RM,Bahari N,et al.G1896A Precore Mutation and Association With HBeAg Status,Genotype and Clinical Status in Patients With Chronic Hepatitis B[J].Hepat Mon,2015,15(10):e31490.
[20]Tornai I.Role of environmental factors in the etiology of hepatocellular carcinoma[J].Orvosi Hetilap,2010,151(28):1132-1136.
[2] Kew M C.Hepatocellular carcinoma:epidemiology and risk factors[J].J Hepatocell Carcinoma,2014,1:115-125.
[3] Yang J D,Roberts L R.Hepatocellular carcinoma:A global view[J].Nat Rev Gastroenterol Hepatol,2010,7(8):448-458.
[4] Ding J,Wang H.Multiple interactive factors in hepatocarcinogenesis[J].Cancer Lett,2014,346(1):17-23.
[5]胡艳芳,王淼,史为涛,等.乙型肝炎病毒前C区基因变异与肝细胞癌相关性的研究[J].中华实验和临床病毒学杂志,2015,29(2):103-105.
[6] Subramaniam A,Shanmugam MK,Perumal E,et al.Potential role of signal transducer and activator of transcription(STAT)3signaling pathway in inflammation,survival,proliferation and invasion of hepatocellular carcinoma[J].Biochim Biophys Acta,2013,1835(1):46-60.
[7]廖明媚,王成志,杨满意,等.JAK2-STAT3信号通路在肝细胞癌中的研究进展[J].中国普通外科杂志,2017,26(1):102-108.
[8] Xie Y,Li J,Zhang C.STAT3promotes the proliferation and migration of hepatocellular carcinoma cells by regulating AKT2[J].Oncol Lett,2018,15(3):3333-3338.
[9] Yang Y,Zheng B,Han Q,et al.Targeting blockage of STAT3inhibits hepatitis B virus-related hepatocellular carcinoma[J].Cancer Biol Ther,2016,17(4):449-456.
[10]Xie J,Zhang Y,Zhang Q,et al.Interaction of signal transducer and activator of transcription 3polymorphisms with hepatitis B virus mutations in hepatocellular carcinoma[J].Hepatology,2013,57(6):2369-2377.
[11]Chanthra N,Payungporn S,Chuaypen N,et al.Single Nucleotide Polymorphisms in STAT3and STAT4and Risk of Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B[J].Asian Pac J Cancer Prev,2015,16(18):8405-8410.
[12]何权瀛,高莹慧.关于吸烟问题若干名词定义[J].中华结核和呼吸杂志,2009,32(1):26-26.
[13]朴金梅,刘梦,李成成,等.STAT4rs7574865GG基因型与GT+TT基因型肝癌患者相关危险因素对比分析[J].中华肿瘤防治杂志,2017,24(2):84-86.
[14]Dondeti MF,El-Maadawy EA,Talaat RM.Hepatitisrelated hepatocellular carcinoma:Insights into cytokine gene polymorphisms[J].World J Gastroenterol,2016,22(30):6800-6816.
[15]Alavi M,Law MG,Grebely J,et al.Time to decompensated cirrhosis and hepatocellular carcinoma after an HBV or HCV notification:A population-based study[J].J Hepatol,2016,65(5):879-887.
[16]Levrero M,Zucman-Rossi J.Mechanisms of HBV-induced hepatocellular carcinoma[J].J Hepatol,2016,64(1Suppl):S84-S101.
[17]Liao Y,Hu X,Chen J,et al.Precore mutation of hepatitis B virus may contribute to hepatocellular carcinoma risk:evidence from an updated meta-analysis[J].PLoS One,2012,7(6):e38394.
[18]曾俊涛,陈静,曾仕平,等.黎族HBV感染者其病毒基因型及C基因启动子/前C区基因突变与肝硬化和肝癌的关系[J].中华肝脏病杂志,2011,19(12):936-938.
[19]Suppiah J,Zain RM,Bahari N,et al.G1896A Precore Mutation and Association With HBeAg Status,Genotype and Clinical Status in Patients With Chronic Hepatitis B[J].Hepat Mon,2015,15(10):e31490.
[20]Tornai I.Role of environmental factors in the etiology of hepatocellular carcinoma[J].Orvosi Hetilap,2010,151(28):1132-1136.