Abstract：
Prostate cancer (PCa) is the most frequent malignancy in male urogenital system around worldwide. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assays were used to assess the biological functions of key genes. Thirty-nine intersecting consensus prognostic genes from five independent cohorts were identified. Subsequently, an eleven-consensus-gene classifier was established. In addition, multivariate Cox regression analyses showed that the classifier served as an independent indicator of recurrence-free survival in three of the five cohorts. Combined receiver operating characteristic (ROC) analysis achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits cell proliferation, while ITGA11 promotes cell migration and invasion, possibly through the PI3K/AKT signaling pathway. To conclude, we established and validated an eleven-consensus-gene classifier, which may add prognostic value to the currently available staging system.
摘要：
前列腺癌（PCa）是全球男性泌尿生殖系统中最常见的恶性肿瘤。我们对PCa患者进行了分子分型和预后评估。包括五个包含1,046名具有RNA表达谱和记录的临床随访信息的PCa患者的队列。单变量,多变量Cox回归分析和最小绝对收缩和选择算子（LASSO）Cox回归用于选择预后基因并建立签名。免疫组织化学染色,细胞增殖，迁移和侵袭试验用于评估关键基因的生物学功能。鉴定了来自五个独立队列的39个相交的共有预后基因。随后，建立了11个共有基因分类器。此外,多变量Cox回归分析显示，分类器在五个队列中的三个队列中作为无复发生存的独立指标。通过将分类器与五个队列中的四个队列的临床病理特征相结合，组合的接收器工作特征（ROC）分析实现了综合效果。SRD5A2抑制细胞增殖，而ITGA11促进细胞迁移和侵袭，可能通过PI3K/AKT信号通路。最后，我们建立并验证了一个十一个共有基因分类器，这可以为当前可用的分期系统增加预后价值。
