【摘要】 目的：研究细胞色素P450与前列腺癌的相关性，通过生物信息挖掘发现细胞色素P450通路与前列腺癌发生发展相关的重要节点。方法：基于3套（GSE46602、GSE32571、GSE70768）前列腺癌数据集筛选差异表达基因，比较关键基因在前列腺癌和正常组织的差异，再结合蛋白表达及病理评分筛选出与前列腺癌发生发展相关联的3个关键节点，并用实时荧光定量PCR(RT-qPCR)进行实验验证。结果：3套全基因组表达谱整合分析找到P450相关的通路存在ALDH3B2、GSTP1、CYP3A5、GSTM1、GSTM5、GSTM2、MGST3等7个差异表达基因（P<0.05,LogFC<-0.5或LogFC>0.5）。结果发现不同Gleason分级仅与其中的6个基因的m RNA表达有相关性（P<0.05）。蛋白表达分析结果显示GSTP1、GSTM1、GSTM5这3个基因的前列腺癌和癌旁组织的蛋白表达差异具有统计学意义（P<0.05）。RT-qPCR验证发现，与前列腺癌旁正常细胞RWPE-1相比，GSTM1和GSTP1在不同的前列腺癌细胞（DU145、C4-2、LNCaP）中mRNA表达下降。GSTM5表达虽然明显降低但差异无统计学意义（P>0.05）。结论：通过多套数据在m RNA和蛋白质表达水平上整合分析发现，P450相关的药物代谢—细胞色素P450通路和细胞色素P450对外来异物的代谢通路与前列腺癌的发生发展存在紧密相关。更多还原

【Abstract】 Objective: To study the importance of cytochrome P450 and prostate cancer, and to discover the important nodes of cytochrome P450 pathway related to the occurrence and development of prostate cancer through bioinformation. Methods: Based on 3 sets of prostate cancer datasets(GSE46602, GSE32571, and GSE70768),the differentially expressed genes were screened, the differences of key genes in prostate cancer and normal tissues were compared, the protein expression and pathological scores were combined to screen out 3 key nodes related to the occurrence and development of prostate cancer, and real-time quantitative PCR(RT-qPCR) was employed to verify the key nodes. Results:The integrated analysis of the three sets of whole-genome expression profiles found that there were seven differentially expressed genes in the P450-related pathways, including ALDH3 B2, GSTP1, CYP3 A5, GSTM1, GSTM5, GSTM2 and MGST3(P<0.05, LogFC<-0.5 or LogFC>0.5). The results showed that different Gleason grades were only related to the mRNA expression of 6 genes(P<0.05). Protein expression analysis results showed that the protein expressions of GSTP1,GSTM1 and GSTM5 genes in prostate cancer and adjacent tissues werestatistically significant. RT-qPCR showed that compared with RWPE-1, the expressions of DU145, C4-2 and LNCaP in GSTP1 and GSTM1 were significantly decreased, while the expression of GSTM5 was not statistically significant(P>0.05). Conclusion: Through the integration and analysis of multiple sets of data at the mRNA and protein expression levels, it is found that P450 related drug metabolism-cytochrome P450 pathway and the cytochrome P450 metabolic pathways of alien invaders is closely related to the occurrence and development of prostate cancer.更多还原