基于生物信息学分析通用转录因子IIH对前列腺癌预后的影响

Bioinformatics-based analysis of the effect of general Transcription Factor IIH on prognosis of Prostate cancer

目的探讨转录起始前复合物中通用转录因子IIH(TFIIH)在前列腺癌(PCa)中的遗传、表达特征及其与PCa预后的关系。方法通过分析癌症基因图谱-PCa数据库(TCGA-PRAD)中495例PCa组织及52例癌旁组织TFIIH亚基的表达特征及临床意义。再通过PCa微阵列芯片验证TFIIH中的关键因子通用转录因子IIH亚基4(GTF2H4)与临床特征[病理分期、生化复发(BCR)以及格里森评分]的相关性。结果495例PCa患者年龄为(61.01±6.82)岁。ERCC3、GTF2H4、MNAT1在格里森评分≥8的PCa组织中mRNA表达量较高(P<0.05)。GTF2H4、MNAT1的表达量与病理分期相关(P<0.05)。高表达GTF2H4的PCa患者的BCR率较高(HR=2.47,95%CI:1.62~3.77,P<0.001),同时其对PCa患者BCR预测效果在各亚基中最好[3、5、7年受试者工作特征曲线下面积(AUC)均>0.7],并在额外4个数据库中得到验证。480例PCa样本中,9例发生了TFIIH亚基的突变,占比1.87%。其中3例为ERCC2亚基突变,2例为GTF2H3亚基突变,GTF2H1、GTF2H4、CCNH、CDK7亚基突变各1例。单因素Cox回归分析显示GTF2H4为BCR的危险因素(HR=2.470,95%CI:1.620~3.767,P<0.001),GTF2H5为保护因素(HR=0.506,95%CI:0.336~0.762,P=0.001)。免疫组织化学染色评分结果显示GTF2H4的蛋白表达量与患者临床特征相关,差异均有统计学意义。结论TFIIH中的关键因子GTF2H4在PCa中高表达并提示预后欠佳。

Objective To investigate the genetic and expression characteristics of transcription factor IIH(TFIIH)in pre-initiationcomplex in prostate cancer(PCa)and its relationship with prostate cancer progression.Methods Analyzing the expression characteristics and clinical signification of TFIIH subunits about 495 cases of PCa and 52 cases of adjacent cancer in The Cancer Genome Atlas-Prostate adenocarcinoma(TCGA-PRAD)database.PCa microarray chip was used to verify the correlation between the key factor General Transcription Factor IIH Subunit 4(GTF2H4)in TFIIH and clinical features.Results The 495 patients with PCa were(61.01±6.82)years old.The mRNA expression of ERCC3、GTF2H4 and MNAT1 were high in PCa tissues with GS≥8(P<0.05).The expression of GTF2H4 and MNAT1 were relevant to the pathological stages(P<0.05).High expression of GTF2H4 has higher biochemical recurrence(BCR)rate in PCa patients(HR=2.47,95%CI:1.62-3.77,P<0.001),which has better predictive effect of BCR in PCa patients(The 3rd,5th,and 7th year AUC all>0.7)than other subunits,and it has been verified in four additional databases.Single-factor Cox regression analysis showed that GTF2H4 were risk factors for BCR(HR=2.470,95%CI:1.620-3.767,P<0.001)and GTF2H5 were protective factors(HR=0.506,95%CI:0.336-0.762,P=0.001).The results of immunohistochemical staining showed that the protein expression of GTF2H4 was correlated with the clinical features of PCa patients.The differences of the above results were statistically significant.Conclusion GTF2H4,the key factor of TFIIH,is highly expressed in PCa and indicates a poor prognosis.