Uncovering citron kinase as a key biomarker for predicting outcomes and therapy efficacy in non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC) is highly heterogeneous, with frequent recurrence and progression. Identifying biomarkers can improve the prediction of therapeutic response and prognosis, guiding clinical decisions. In this study, public NMIBC databases were analyzed for differential expression, receiver operating characteristic (ROC), Cox regression, and Kaplan-Meier survival to identify and validate potential prognostic biomarkers of NMIBC. Functional enrichment analysis was conducted to reveal the potential molecular mechanisms of hub genes. Bioinformatics findings were validated through immunohistochemistry (IHC) and in vitro experiments. Immune cell infiltration and drug sensitivity analyses were performed to assess differences between low- and high-CIT expression groups. Citron kinase (CIT) was identified as a biomarker linked to aggressive tumors and poor prognosis in NMIBC patients. CIT overexpression predicts poor intravesical Bacillus Calmette-Guérin (BCG) efficacy in patients with NMIBC. Immunohistochemical staining demonstrated that the protein expression analysis of CIT was consistent with the mRNA analysis results. Functional enrichment analysis revealed that the function of CIT is associated with tumor development and progression. Furthermore, in vitro cell experiments demonstrated that CIT knockdown inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase via downregulation of cyclin dependent kinase 1. Immune infiltration analysis revealed that high CIT expression contributed to BCG resistance by reducing CD8+ T cell infiltration in the NMIBC microenvironment. Additionally, drug sensitivity analysis further demonstrated that high CIT expression leads to resistance to common chemotherapy drugs, including epirubicin, gemcitabine, and cisplatin. This study identifies CIT as a promising biomarker, offering a foundation for prognostic evaluation and personalized therapeutic strategies for NMIBC patients.