DOI: 10.6084/m9.figshare.30197543.v1
title: Downregulated of CTGF reveals mechanism, remodels immune microenvironment, modulates drug sensitivity in bladder cancer

description: This study aims to investigate the expression profile, molecular mechanisms, and biological functions of Connective Tissue Growth Factor (CTGF) in bladder cancer (BLCA). 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. 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 (<i>p</i> &lt; 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). 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. Bladder cancer (BLCA) is a common type of cancer, and despite the availability of multiple treatment approaches, its recurrence rate remains high. This study investigated a molecule named Connective Tissue Growth Factor (CTGF) to explore its potential as a biomarker or therapeutic target for BLCA treatment. Databases, such as TCGA, GEO, and HPA were utilized to examine the levels of CTGF in BLCA tissues. Additionally, computational tools were employed to investigate how CTGF regulates the progression of BLCA, immune infiltration in cancer tissues, and drug efficacy. Our results indicated that CTGF are significantly lower in BLCA tissues than in normal tissues. Mechanistic analysis suggested that CTGF and its related genes are involved in processes, such as motility, invasion, and regulation of the tumor microenvironment. Furthermore, there were notable differences in the types of immune cell infiltration in BLCA tissues with varying CTGF expression levels, suggesting that CTGF is involved in the regulation between stromal control and immune response. Finally, drug sensitivity analysis revealed that CTGF expression was positively correlated with sensitivity to EGFR inhibitors (e.g., Afatinib) and negatively correlated with resistance to PARP inhibitors (e.g., Olaparib). Overall, CTGF may be a valuable biomarker or target for BLCA treatment, but further research is needed to fully understand its clinical application. Unlike most solid tumors, in BLCA, we found that CTGF is significantly downregulated at both mRNA transcription and protein levels, and high CTGF expression is associated with poor patient prognosis.It was found that significant differences in CTGF expression were observed across different patient’s ages, genders, pathological stages, tumor sizes (T), and lymph node metastasis (N).There are significant differences in the infiltration levels of CD4+ T cells, M0/M1/M2 macrophages, B cells, and other immune cells in BLCA tissues with varying CTGF expression levels.CTGF expression levels are positively correlated with sensitivity to EGFR inhibitors (e.g., Afatinib) and negatively correlated with sensitivity to PARP inhibitors (e.g., Olaparib).These findings suggest that CTGF is associated with immune infiltration and drug therapy in BLCA, strongly supporting CTGF as a promising potential therapeutic target. Unlike most solid tumors, in BLCA, we found that CTGF is significantly downregulated at both mRNA transcription and protein levels, and high CTGF expression is associated with poor patient prognosis. It was found that significant differences in CTGF expression were observed across different patient’s ages, genders, pathological stages, tumor sizes (T), and lymph node metastasis (N). There are significant differences in the infiltration levels of CD4+ T cells, M0/M1/M2 macrophages, B cells, and other immune cells in BLCA tissues with varying CTGF expression levels. CTGF expression levels are positively correlated with sensitivity to EGFR inhibitors (e.g., Afatinib) and negatively correlated with sensitivity to PARP inhibitors (e.g., Olaparib). These findings suggest that CTGF is associated with immune infiltration and drug therapy in BLCA, strongly supporting CTGF as a promising potential therapeutic target.