Stem Cell–Related Gene CALR as a Novel Prognostic Factor for Bladder Cancer: Implications for Immunotherapy

Cancer stem cells (CSCs) are a unique category of cells located within tumors, characterized by their exceptional self-renewal abilities and capacity to differentiate into different types of tumor cells. These cells are crucial in processes such as tumor metastasis, recurrence, and resistance to treatment. Nevertheless, their particular roles in bladder urothelial carcinoma (BLCA) require deeper exploration. This investigation firstly assessed the relationships between genes associated with CSCs and both the prognostic outcomes and responses to immunotherapy in patients with BLCA using cluster analysis methods. Among the genes linked to stem cells, CALR was identified as the most notable prognostic marker by the XGBoost algorithm. Additionally, the study explored the correlation between CALR and immune cell infiltration, as well as its interaction with mitomycin using molecular docking methods. In vitro experiments further validated that CALR affects BLCA stem cells. Utilizing multiple machine learning approaches, this study identified 14 essential stem cell-associated genes, underscoring their significance for BLCA diagnosis and potential therapeutic targeting. Critically, CALR demonstrates a strong correlation with prognostic outcomes and immunotherapy responses in BLCA, consistent with experimental findings indicating its elevated expression in BLCA and association with poor prognosis. Laboratory investigations have demonstrated that reducing CALR expression can lessen the stemness features of BLCA. Our results highlight the critical role of genes related to stem cells in BLCA and identify CALR as a promising target associated with stem cell functionality.