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Chloride intracellular channel protein 2: prognostic marker and correlation with PD-1/PD-L1 in breast cancer
Tao Xu1,2, Zhi Wang2, Menglu Dong1
1Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of HUST, Wuhan 430030, Hubei, People's Republic of China.
Abstract:
Immune checkpoint inhibition has emerged as an effective treatment for multiple solid tumors, including advanced-stage breast cancer (BC). During the past decade, the US Food and Drug Administration has approved a number of agents for immune checkpoint blockade (ICB). However, the limited data on monotherapy anti-tumor activity in BC underscores the need for robust predictive biomarker development. Here, we used weighted gene coexpression network analysis of genes differentially expressed between BC and normal tissue to identify genes coexpressed with programmed death-1 (PD-1) and its ligand (PD-L1). Tumor Immune Estimation Resource and Gene Expression Profiling Interaction Analysis were used to assess the relationship between gene expression and the abundance of tumor-infiltrating lymphocytes (TILs). We found that chloride intracellular channel protein 2 (CLIC2) was not only coexpressed with PD-1 and PD-L1, but its increased expression was associated with a favorable prognosis and enrichment of multiple TIL types, particularly CD8+ T cells. These results suggest that CLIC2 is a potentially useful biomarker for identifying BC patients who could benefit from ICB.
Insights
Chloride intracellular channel protein 2 (CLIC2) shows promise as a biomarker for breast cancer (BC) patients. Increased CLIC2 expression correlates with better prognosis and more tumor-infiltrating lymphocytes, suggesting benefit from immune checkpoint blockade therapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint inhibition (ICI) is effective for various solid tumors, including advanced breast cancer (BC).
- Limited data on ICI monotherapy efficacy in BC highlights the need for predictive biomarkers.
- The US FDA has approved several immune checkpoint blockade (ICB) agents.
Purpose of the Study:
- To identify novel predictive biomarkers for BC patients undergoing ICB therapy.
- To investigate the coexpression patterns of programmed death-1 (PD-1) and its ligand (PD-L1) with other genes in BC.
- To assess the relationship between gene expression, prognosis, and tumor-infiltrating lymphocytes (TILs) in BC.
Main Methods:
- Weighted gene coexpression network analysis (WGCNA) was employed to identify genes coexpressed with PD-1 and PD-L1.
- Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) were utilized to analyze gene expression and TILs.
- Differential gene expression analysis between BC and normal tissues was performed.
Main Results:
- Chloride intracellular channel protein 2 (CLIC2) was found to be coexpressed with PD-1 and PD-L1.
- Increased CLIC2 expression was associated with a favorable patient prognosis.
- Higher CLIC2 levels correlated with increased abundance of multiple TIL types, notably CD8+ T cells.
Conclusions:
- CLIC2 is a potential predictive biomarker for identifying BC patients who may respond to ICB.
- CLIC2 expression levels can indicate a favorable prognosis and a robust anti-tumor immune response in BC.
- Further validation of CLIC2 as a biomarker for ICB therapy in BC is warranted.
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