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Combined Conditional Knockdown and Adapted Sphere Formation Assay to Study a Stemness-Associated Gene of Patient-derived Gastric Cancer Stem Cells
Published on: May 9, 2020
CD2AP shapes a stromal reduced tumor microenvironment and contributes to immunotherapy in gastric cancer
Haoliang Li1,2, Hua Chen3, Ting Zhao2
1Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Abstract:
Gastric cancer (GC) ranks as the fifth most prevalent malignant tumor and stands as the fourth leading contributor to cancer-related fatalities on a global scale. The specific link between CD2 Associated Protein (CD2AP) expression and the tumor microenvironment (TME) remains unclear, and further exploration is needed to understand its potential role in immune response and as a target for immunotherapy in GC. Utilizing RNA sequencing data acquired from The Cancer Genome Atlas (TCGA) for a pan-cancer analysis, a comprehensive evaluation was carried out to determine the expression pattern and immunological involvement of CD2AP. Systematic association of CD2AP with immunological features within the stomach adenocarcinoma (STAD) TME was subsequently performed, encompassing factors like cancer immunity cycles, immune checkpoints, immunomodulators, tumor-infiltrating immune cells (TIICs). We found that CD2AP was enhanced expression in the TME of a variety of malignancies. CD2AP contributes to forming a stromal reduced TME in GC and improve the efficacy of immunotherapy. It was observed that patients with elevated levels of CD2AP, along with high scores on their CD4, CD20, and CD57 immune markers, tended to experience the most favorable prognosis. Furthermore, an IRS was constructed to accurately assess the prognosis of STAD patients. Since CD2AP was associated with the formation of stromal reduced TME in STAD, the expression of CD2AP can improve the effect of immunotherapy of STAD. CD2AP could emerge as a novel prognostic biomarker for STAD, offering a fresh avenue for molecular targeted therapy.
Insights
CD2 Associated Protein (CD2AP) enhances immunotherapy efficacy in gastric cancer by reducing stromal presence in the tumor microenvironment. Elevated CD2AP expression correlates with improved patient prognosis and offers a new target for gastric cancer therapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality worldwide.
- The role of CD2 Associated Protein (CD2AP) in the gastric cancer tumor microenvironment (TME) and its impact on immunotherapy are not well understood.
Purpose of the Study:
- To investigate the expression patterns and immunological significance of CD2AP in the TME of various cancers, with a focus on stomach adenocarcinoma (STAD).
- To explore the association of CD2AP with immune features and its potential as a prognostic biomarker and therapeutic target in STAD.
Main Methods:
- Pan-cancer analysis using RNA sequencing data from The Cancer Genome Atlas (TCGA).
- Systematic association of CD2AP expression with immunological factors in the STAD TME, including cancer immunity cycles, immune checkpoints, immunomodulators, and tumor-infiltrating immune cells (TIICs).
- Construction of an Immune Risk Score (IRS) to assess STAD patient prognosis.
Main Results:
- CD2AP expression was found to be elevated in the TME of multiple malignancies.
- In GC, CD2AP contributes to a stromal-reduced TME, enhancing immunotherapy effectiveness.
- Higher CD2AP levels, along with elevated CD4, CD20, and CD57 immune markers, were linked to a significantly better prognosis in STAD patients.
Conclusions:
- CD2AP expression is associated with a stromal-reduced TME in STAD and can improve immunotherapy outcomes.
- CD2AP shows promise as a novel prognostic biomarker for STAD.
- CD2AP represents a potential new avenue for molecular targeted therapy in gastric cancer.
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