Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer

Abstract

Background: Bladder cancer (BLCA) is a malignant tumor with a dismay outcome. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. Therefore, we aimed to explore the function and prognostic value of CRs in BLCA patients. Methods: Chromatin regulators (CRs) were acquired from the previous top research. The mRNA expression and clinical information were downloaded from TCGA and GEO datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to select the prognostic gene and construct the risk model for predicting outcome in BLCA. The Kaplan-Meier analysis was used to assess the prognosis between high- and low-risk groups. We also investigated the drug sensitivity difference between high- and low-risk groups. CMAP dataset was performed to screen the small molecule drugs for treatment. Results: We successfully constructed and validated an 11 CRs-based model for predicting the prognosis of patients with BLCA. Moreover, we also found 11 CRs-based model was an independent prognostic factor. Functional analysis suggested that CRs were mainly enriched in cancer-related signaling pathways. The CR-based model was also correlated with immune cells infiltration and immune checkpoint. Patients in the high-risk group were more sensitive to several drugs, such as mitomycin C, gemcitabine, cisplatin. Eight small molecule drugs could be beneficial to treatment for BLCA patients. Conclusion:: In conclusion, our study provided novel insights into the function of CRs in BLCA. We identified a reliable prognostic biomarker for the survival of patients with BLCA.