Although postoperative platinum-based chemotherapy can improve the prognosis of afflicted patients, resistance to chemotherapeutic drugs is still a difficulty faced in BLCA treatment. Currently, surgical resection remains the first treatment of choice for patients with BLCA. Furthermore, with the aging of the global population, the morbidity related to this urinary system disease is increasing annually. There are about 573,000 cases of BLCA worldwide, with 212,000 deaths. The main type of BLCA is uroepithelial carcinoma, which is clinically classified into non-basal-invasive and muscle-invasive subtypes.
Introductionīladder cancer (BLCA), which represents the tenth most common types of cancer worldwide, is the predominant malignancy of the urinary system. This study highlights the crucial role of the CSR signature in bladder cancer and provides a CRS model for accurate predictions of the disease prognosis and chemotherapy and immunotherapy responses. Notably, the CSR-related gene ANLN was positively correlated with CD8 + immune cell infiltration, PD-L1 expression, and sensitivity to PD-L1 inhibitors and could thus provide guidance for clinical immunotherapy.
Inflammatory signalling pathways (e.g., inflammatory response, TNFA signalling via NFƘB, IFN α response, and IL2-STAT5 signalling) were markedly upregulated in patients with high CRS. The CRS could predict the malignant phenotype, chemotherapeutic efficacy, immune invasion, and disease prognosis. Next, we developed a common serum response (CSR) risk score (CRS) model based on fibroblast CSR genes and systematically analysed the correlations of these genes or the CRSs with survival, previously reported molecular subtypes, clinicopathological features, cancer signalling pathways, chemotherapeutic responses, and the tumour microenvironment using TCGA and validation cohorts. We analysed the variations in 189 oncogenic signature gene sets between normal and tumourous tissues from The Cancer Genome Atlas (TCGA) and found that the “CSR_LATE_UP” signature was the most upregulated oncogenic signature gene set in bladder cancer. Abnormal oncogenic signatures provide important clues regarding cancer prognosis and treatment.