Abstract
BACKGROUND: This study aims to investigate the expression profile, molecular mechanisms, and biological functions of Connective Tissue Growth Factor (CTGF) in bladder cancer (BLCA). METHODS: For accurate CTGF mRNA expression assessment, 1728 samples were collected. Additionally, for uncovering potential signaling pathways, differentially co-expressed CTGF genes were employed. For exploring CTGF's effects, its impact on immune microenvironment and drug sensitivity was studied. RESULTS: CTGF mRNA was significantly underexpressed in BLCA (standardized mean difference [SMD] = -1.06, 95% CI: -1.89-0.23), and this downregulation was confirmed at the protein level (p < 0.0001). CTGF was mainly involved in immune microenvironment-related pathways and biological processes (BPs) associated with stromal remodeling and extracellular matrix dynamics. Moreover, A statistically significant correlation was identified between the expression levels of CTGF and the infiltration degrees of variety of immune cells. Notably, CTGF expression was positively correlated with sensitivity to EGFR inhibitors (e.g., Afatinib) and negatively correlated with resistance to PARP inhibitors (e.g., Olaparib). CONCLUSIONS: This study elucidated the low expression of CTGF in BLCA. CTGF may promotes tumor progression by remodeling the immune microenvironment and extracellular matrix. Additionally, its expression is positively correlated with sensitivity to EGFR inhibitors and negatively correlated with resistance to PARP inhibitors.