Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Guoxue Xiang #37, Chengdu, 610041, People's Republic of China.
Department of Urology, Chengdu Second People's Hospital, Chengdu, China.
Sci Rep. 2023 Jun 3;13(1):9016. doi: 10.1038/s41598-023-36125-0.
Current evidence indicate that cancer-associated fibroblasts (CAFs) play an important role in prostate cancer (PCa) development and progression. In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.
目前的证据表明，癌相关成纤维细胞（CAFs）在前列腺癌（PCa）的发展和进展中起着重要作用。在这项研究中，我们通过整合单细胞和批量 RNA 测序数据，确定了接受根治性前列腺切除术的 PCa 患者的 CAF 相关分子亚型和预后指数。我们使用软件 R 3.6.3 及其合适的软件包完成了分析。通过单细胞和批量 RNA 测序分析，使用 NDRG2、TSPAN1、PTN、APOE、OR51E2、P4HB、STEAP1 和 ABCC4 构建了分子亚型和 CAF 相关基因预后指数（CRGPI）。这些基因可以在 TCGA 数据库中清楚地将 PCa 患者分为两种亚型，并且亚型 1 的 BCR 风险比亚型 2 高 13.27 倍，具有统计学意义。在 MSKCC2010 和 GSE46602 队列中也观察到了类似的结果。此外，分子亚型是 PCa 患者的独立危险因素。我们基于上述基因构建了 CRGPI，并根据该评分的中位数将 TCGA 数据库中的 430 名 PCa 患者分为高风险和低风险组。我们发现，高风险组的 BCR 风险明显高于低风险组（HR：5.45）。对于功能分析，蛋白分泌在亚型 2 中高度富集，而囊泡运输中的 snare 相互作用在亚型 1 中高度富集。在肿瘤异质性和干性方面，亚型 1 的 TMB 水平明显高于亚型 2。此外，亚型 1 的激活树突状细胞评分明显高于亚型 2。基于 8 个 CAF 相关基因，我们开发了两种预后亚型，并构建了一个基因预后指数，该指数可以很好地预测 PCa 患者的预后。
