Department of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Jianshan Street, Hexi, Tianjin, 300211, People's Republic of China.
Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Tianjin, 300211, China.
BMC Med Genomics. 2023 Oct 26;16(1):264. doi: 10.1186/s12920-023-01678-6.
Tumor Metabolism is strongly correlated with prognosis. Nevertheless, the prognostic and therapeutic value of metabolic-associated genes in BCa patients has not been fully elucidated. First, in this study, metabolism-related differential expressed genes DEGs with prognostic value in BCa were determined. Through the consensus clustering algorithm, we identified two molecular clusters with significantly different clinicopathological features and survival prognosis. Next, a novel metabolism-related prognostic model was established. Its reliable predictive performance in BCa was verified by multiple external datasets. Multivariate Cox analysis exhibited that risk score were independent prognostic factors. Interestingly, GSEA enrichment analysis of GO, KEGG, and Hallmark gene sets showed that the biological processes and pathways associated with ECM and collagen binding in the high-risk group were significantly enriched. Notely, the model was also significantly correlated with drug sensitivity, immune cell infiltration, and immunotherapy efficacy prediction by the wilcox rank test and chi-square test. Based on the 7 immune infiltration algorithm, we found that Neutrophils, Myeloid dendritic cells, M2 macrophages, Cancer-associated fibroblasts, etc., were more concentrated in the high-risk group. Additionally, in the IMvigor210, GSE111636, GSE176307, or our Truce01 (registration number NCT04730219) cohorts, the expression levels of multiple model genes were significantly correlated with objective responses to anti-PD-1/anti-PD-L1 immunotherapy. Finally, the expression of interested model genes were verified in 10 pairs of BCa tissues and para-carcinoma tissues by the HPA and real-time fluorescent quantitative PCR. Altogether, the signature established and validated by us has high predictive power for the prognosis, immunotherapy responsiveness, and chemotherapy sensitivity of BCa.
肿瘤代谢与预后密切相关。然而，代谢相关基因在 BCa 患者中的预后和治疗价值尚未完全阐明。首先，在本研究中，确定了具有 BCa 预后价值的代谢相关差异表达基因 DEGs。通过共识聚类算法，我们鉴定了两个具有显著不同临床病理特征和生存预后的分子簇。接下来，建立了一个新的代谢相关预后模型。通过多个外部数据集验证了其在 BCa 中的可靠预测性能。多变量 Cox 分析表明，风险评分是独立的预后因素。有趣的是，GO、KEGG 和 Hallmark 基因集的 GSEA 富集分析表明，高风险组与 ECM 和胶原结合相关的生物学过程和途径显著富集。值得注意的是，该模型与药物敏感性、免疫细胞浸润和免疫治疗疗效预测也显著相关，Wilcox 秩检验和卡方检验结果均具有统计学意义。基于 7 种免疫浸润算法，我们发现中性粒细胞、髓样树突状细胞、M2 巨噬细胞、癌相关成纤维细胞等在高风险组中更为集中。此外，在 IMvigor210、GSE111636、GSE176307 或我们的 Truce01（注册号 NCT04730219）队列中，模型基因的表达水平与抗 PD-1/抗 PD-L1 免疫治疗的客观反应显著相关。最后，通过 HPA 和实时荧光定量 PCR 验证了 10 对 BCa 组织和癌旁组织中感兴趣模型基因的表达。总之，我们建立和验证的特征对 BCa 的预后、免疫治疗反应性和化疗敏感性具有较高的预测能力。
