Bladder cancer is associated with increased risk of systemic inflammatory complications: evidence from a propensity score-matched cohort study and transcriptomic analysis

Background Emerging evidence indicates that malignancies can exert systemic effects extending beyond the primary tumor site. Bladder cancer, a common urological malignancy, may predispose patients to chronic inflammation and immune dysregulation, yet population-based evidence remains limited. Methods A dual-database analysis was conducted by integrating epidemiologic data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018) with transcriptomic datasets from the Gene Expression Omnibus (GEO). Adults aged ≥45 years with available diagnostic, metabolic, and inflammatory information were included. Propensity score matching (1:1) was applied based on demographic, metabolic, and lifestyle covariates. The primary endpoint was the occurrence of systemic inflammatory events, assessed using weighted Kaplan–Meier and Cox proportional hazards models. Differentially expressed genes (DEGs) between bladder cancer and adjacent normal tissues were identified from GEO datasets, followed by Gene Ontology (GO) and KEGG enrichment analyses. Machine-learning algorithms (LASSO, random forest, and SVM-RFE) were used to identify inflammation-related hub genes. Results During a median follow-up of 3.6 years, participants with bladder cancer exhibited a significantly higher incidence of systemic inflammatory events compared with matched controls (10.9% vs 3.1%, p < 0.001; HR 3.67, 95% CI 2.75–4.59). Transcriptomic profiling identified 599 DEGs (312 upregulated, 287 downregulated), enriched in immune-metabolic pathways such as PI3K-Akt, IL-17, and cytokine–receptor interactions. Key hub genes— ND6 , CD38 , SERPINE1 , and EPHX2 —emerged as potential molecular mediators linking metabolic dysregulation with inflammatory signaling. Conclusions Integrating CHARLS epidemiologic findings with GEO transcriptomic validation provides convergent evidence that bladder cancer is independently associated with increased systemic inflammatory burden. These results highlight a potential immunometabolic axis underlying tumor-related inflammation and identify molecular targets that may guide early risk stratification and anti-inflammatory interventions. Impact The involvement of immunometabolic dysregulation and highlighting novel molecular signatures may inform future risk stratification and therapeutic targeting in this population.