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Published on: October 30, 2013
Downregulated of CTGF reveals mechanism, remodels immune microenvironment, modulates drug sensitivity in bladder
Hanjie Zhang1, Kaiqiang Tang2, Yiyang Chen1
1Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
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.
Insights
Connective Tissue Growth Factor (CTGF) is underexpressed in bladder cancer (BLCA), potentially promoting tumor progression by altering the immune microenvironment and extracellular matrix. CTGF levels indicate sensitivity to EGFR inhibitors and resistance to PARP inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Connective Tissue Growth Factor (CTGF) is implicated in various cancers.
- Its role in bladder cancer (BLCA) requires further elucidation.
- Understanding CTGF's function is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression profile of CTGF in BLCA.
- To explore the molecular mechanisms and biological functions of CTGF in BLCA.
- To determine the association of CTGF with the tumor immune microenvironment and drug sensitivity.
Main Methods:
- Analysis of CTGF mRNA expression in 1728 BLCA samples.
- Identification of differentially co-expressed CTGF genes to uncover signaling pathways.
- Assessment of CTGF's impact on immune cell infiltration and drug sensitivity.
Main Results:
- CTGF mRNA was significantly underexpressed in BLCA (SMD = -1.06).
- CTGF is involved in immune microenvironment pathways, stromal remodeling, and extracellular matrix dynamics.
- CTGF expression correlated with immune cell infiltration, sensitivity to EGFR inhibitors, and resistance to PARP inhibitors.
Conclusions:
- CTGF is downregulated in BLCA and may promote tumor progression.
- CTGF influences the tumor immune microenvironment and extracellular matrix.
- CTGF expression serves as a predictive biomarker for EGFR and PARP inhibitor sensitivity.
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