The aim of this study was to validate prostate cancer‐associated genes on transcript level and to assess the prognostic value of the most promising markers by immunohistochemistry. Based on differentially expressed genes found in a previous study, 84 genes were further validated using mRNA expression data and follow‐up information from the Cancer Genome Atlas (TCGA) prostate cancer cohort (n = 497). Immunohistochemistry was used for validation of three genes in an independent, clinically annotated prostatectomy patient cohort (n = 175) with biochemical relapse as endpoint. Also, associations with clinicopathological variables were evaluated. Eleven protein‐coding genes from the list of 84 genes were associated with biochemical recurrence‐free survival on mRNA expression level in multivariate Cox‐analyses. Three of these genes (TSPAN1, ESRP1 and KIAA1324) were immunohistochemically validated using an independent cohort of prostatectomy patients. Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence‐free survival. TSPAN1 was univariately prognostic but failed significance on multivariate analysis, probably due to its strong correlation with high Gleason scores. Multistep filtering using the publicly available TCGA cohort, data of an earlier expression profiling study which profiled 3023 cancer‐associated transcripts in 42 primary prostate cancer cases, identified two novel candidate prognostic markers (ESRP1 and KIAA1324) of primary prostate cancer for further study.

中文翻译：

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TSPAN1，KIAA1324和ESRP1在前列腺癌中的预后作用

这项研究的目的是在转录水平上验证前列腺癌相关基因，并通过免疫组织化学评估最有前途的标志物的预后价值。根据先前研究中发现的差异表达基因，使用mRNA表达数据和癌症基因组图谱（TCGA）前列腺癌队列（n  = 497）的随访信息进一步验证了84个基因。免疫组织化学用于验证独立的，临床注释的前列腺切除术患者队列中的三个基因（n = 175），生化复发为终点。此外，与临床病理变量的关联进行了评估。在多变量Cox分析中，来自84个基因的列表中的11个蛋白质编码基因与mRNA表达水平上无生化复发的生存率相关。这些基因中的三个（TSPAN1，ESRP1和KIAA1324）使用独立的前列腺切除术患者队列进行了免疫组织化学验证。ESRP1和KIAA1324均独立于无生化复发的生存期。TSPAN1是单因素预后的，但在多变量分析中没有显着意义，这可能是由于TSPAN1与高Gleason评分有很强的相关性。使用公开的TCGA队列进行多步过滤，这是一项较早的表达谱研究的数据，该研究对42例原发性前列腺癌病例中的3023种与癌症相关的转录本进行了分析，确定了两种新的原发性前列腺癌候选预后标志物（ESRP1和KIAA1324）有待进一步研究。