Abstract:
Molecular heterogeneity in prostate cancer (PCa) is one of the key reasons underlying the differing likelihoods of recurrence after surgical treatment in individual patients of the same clinical category. In this study, we performed RNA-Seq profiling of 58 localized PCa and 43 locally advanced PCa tissue samples obtained as a result of radical prostatectomy on a cohort of Russian patients. Based on bioinformatics analysis, we examined features of the transcriptome profiles within the high-risk group, including within the most commonly represented molecular subtype, TMPRSS2-ERG. The most significantly affected biological processes in the samples were also identified, so that they may be further studied in the search for new potential therapeutic targets for the categories of PCa under consideration. The highest predictive potential was found with the EEF1A1P5, RPLP0P6, ZNF483, CIBAR1, HECTD2, OGN, and CLIC4 genes. We also reviewed the main transcriptome changes in the groups at intermediate risk of PCa-Gleason Score 7 (groups 2 and 3 according to the ISUP classification)-on the basis of which the LPL, MYC, and TWIST1 genes were identified as promising additional prognostic markers, the statistical significance of which was confirmed using qPCR validation.
摘要:
前列腺癌(PCa)的分子异质性是同一临床类别的个体患者手术治疗后复发可能性不同的关键原因之一。在这项研究中,我们对一组俄罗斯患者行根治性前列腺切除术后获得的58份局部PCa和43份局部晚期PCa组织样本进行了RNA-Seq分析.基于生物信息学分析,我们检查了高危人群的转录组特征,包括最常见的分子亚型,TMPRSS2-ERG。还确定了样品中受影响最严重的生物过程,因此可以进一步研究它们,以寻找正在考虑的PCa类别的新的潜在治疗靶标。EEF1A1P5,RPLP0P6,ZNF483,CIBAR1,HECTD2,OGN,和CLIC4基因。我们还回顾了PCa-Gleason评分7(根据ISUP分类的第2组和第3组)处于中等风险的组的主要转录组变化-在此基础上,LPL,MYC,和TWIST1基因被鉴定为有希望的额外预后标志物,使用qPCR验证证实了其统计学意义.