Department of Chemoradiotherapy, The Affiliated People's Hospital of Ningbo University, Ningbo, China.
Department of Gastroenterology, The Affiliated People's Hospital of Ningbo University, Ningbo, China.
Mol Biotechnol. 2024 Sep;66(9):2532-2547. doi: 10.1007/s12033-023-00892-y. Epub 2023 Sep 25.
Bladder cancer was one of the most common carcinomas around the world. However, the mechanism of the disease still remained to be investigated. We expected to establish a prognostic survival model with 9 prognostic genes to predict overall survival (OS) in patients of bladder cancer. The gene expression data of bladder cancer were obtained from TCGA and GEO datasets. TCGA and GEO datasets were used for screening prognostic genes along with developing and validating a 9-gene prognostic survival model by method of weighted gene co-expression network analysis (WGCNA) and LASSO with Cox regression. The relative analysis of evaluate tumor burden mutation (TBM), GO, KEGG, chemotherapy drug and functional pathway were also performed based on CAF-related mRNAs. 151 Overlapping CAF-related genes were distinguished after intersecting differentially expressed genes from 945 genes in TCGA and 491 genes in GEO dataset. 9 Prognostic genes (MSRB2, AGMAT, KLF6, DDAH2, GADD45B, SERPINE2, STMN3, TEAD2, and COMP) were used for construction of prognostic model after LASSO with Cox regression. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Functional analysis indicated chemokine, cytokine, ECM interaction, oxidative stress and apoptosis were highly appeared. Potential drugs targeted different CAF-related genes like vemurafenib, irofulven, ghiotepa, and idarubicin were found as well. We constructed a novel 9 CAF-related mRNAs prognostic model and explored the gene expression and potential functional information of related genes, which might be worthy of clinical application. In addition, potential chemotherapy drugs could provide useful insights into the potential clinical treatment of bladder cancer.
膀胱癌是全球最常见的癌种之一。然而,其发病机制仍有待研究。我们期望建立一个包含 9 个预后基因的预后生存模型,以预测膀胱癌患者的总生存期(OS)。从 TCGA 和 GEO 数据集获得膀胱癌的基因表达数据。采用加权基因共表达网络分析(WGCNA)和 LASSO 与 Cox 回归相结合的方法,筛选预后基因,建立和验证 9 个基因预后生存模型。还基于 CAF 相关 mRNAs 对评估肿瘤负荷突变(TBM)、GO、KEGG、化疗药物和功能途径进行了相关分析。在 TCGA 中 945 个基因和 GEO 数据集 491 个基因的差异表达基因相交后,确定了 151 个重叠的 CAF 相关基因。经过 LASSO 与 Cox 回归的筛选,确定了 9 个预后基因(MSRB2、AGMAT、KLF6、DDAH2、GADD45B、SERPINE2、STMN3、TEAD2 和 COMP)用于构建预后模型。该模型的受试者工作特征(ROC)曲线显示了良好的生存预测。功能分析表明,趋化因子、细胞因子、细胞外基质相互作用、氧化应激和细胞凋亡等途径显著富集。还发现了针对不同 CAF 相关基因的潜在药物,如 vemurafenib、irofulven、ghiotepa 和伊达比星。我们构建了一个新的 9 个 CAF 相关 mRNAs 预后模型,并探索了相关基因的基因表达和潜在功能信息,这可能值得临床应用。此外,潜在的化疗药物可能为膀胱癌的潜在临床治疗提供有用的见解。