Department of Urology, The First Affiliated Hospital of Anhui Medical University, 218th Jixi Road, 230022, Hefei, Anhui, People's Republic of China.
Institute of Urology, Anhui Medical University, 218th Jixi Road, 230022, Hefei, Anhui, People's Republic of China.
Commun Biol. 2022 Mar 15;5(1):233. doi: 10.1038/s42003-022-03164-8.
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.
前列腺癌(PCa)是全球男性泌尿生殖系统最常见的恶性肿瘤。我们对前列腺癌患者进行了基于共识基因的分子亚型和预后评估。本研究纳入了 5 个包含 1046 例 PCa 患者 RNA 表达谱和记录临床随访信息的队列。采用单因素、多因素 Cox 回归分析和最小绝对收缩和选择算子(LASSO)Cox 回归分析筛选预后基因并建立特征模型。免疫组织化学染色、细胞增殖、迁移和侵袭实验用于评估关键基因的生物学功能。从 5 个独立队列中鉴定出 39 个重叠的共识预后基因。随后建立了一个由 11 个共识基因组成的分类器。此外,多因素 Cox 回归分析显示,该分类器在 5 个队列中的 3 个队列中是无复发生存的独立预测指标。在 5 个队列中的 4 个队列中,结合接受者操作特征(ROC)分析,通过将分类器与临床病理特征相结合,可以获得综合效果。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。总之,我们建立并验证了一个由 11 个共识基因组成的分类器,该分类器可能为现有的分期系统增加预后价值。