Characterization and verification of CD81 as a potential target in lung squamous cell carcinoma
Xifu Ye1, Junyuan Deng1, Chengyuan Dong2
1Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Abstract:
CD81 is a cell surface transmembrane protein of the tetraspanin family, which critically regulates signal transduction and immune response. Growing evidence has shown that CD81 plays important roles in tumorigenesis and influences immunotherapy response. Here, combining bio-informatics and functional analysis, we find that CD81 is a risk factor in lung squamous cell carcinoma (LUSC), whereas a protective factor in lung adenocarcinoma. In LUSC with high expression of CD81, the autophagy and JAK-STAT signaling pathway are activated. Meanwhile, the expression level of CD81 is negatively correlated with tumor mutational load (TMB), microsatellite instability (MSI), and neoantigen (NEO). Furthermore, patients with LUSC and high expression of CD81 do not respond to immunotherapy drugs, but can respond to chemotherapy drugs. Importantly, depletion of CD81 suppresses the proliferation of LUSC cell, and enhances the sensitivity to cisplatin. Our findings suggest that CD81 represents a potential target for cisplatin-based chemotherapy in patients with LUSC.
Insights
CD81 protein is a risk factor in lung squamous cell carcinoma (LUSC), promoting tumor growth and hindering immunotherapy. Targeting CD81 may improve chemotherapy response in LUSC patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- CD81, a tetraspanin protein, regulates cell signaling and immune responses.
- CD81 influences cancer development and response to immunotherapy.
Purpose of the Study:
- Investigate the role of CD81 in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma.
- Determine CD81's impact on tumor characteristics and treatment response in LUSC.
Main Methods:
- Bio-informatic analysis of gene expression data.
- Functional experiments involving CD81 depletion in LUSC cells.
Main Results:
- CD81 acts as a risk factor in LUSC but a protective factor in lung adenocarcinoma.
- High CD81 expression in LUSC correlates with activated autophagy and JAK-STAT signaling.
- CD81 negatively correlates with tumor mutational burden, microsatellite instability, and neoantigens in LUSC.
- LUSC patients with high CD81 do not respond to immunotherapy but may benefit from chemotherapy.
- CD81 depletion inhibits LUSC cell proliferation and increases sensitivity to cisplatin.
Conclusions:
- CD81 is a potential therapeutic target for cisplatin-based chemotherapy in LUSC.
- Modulating CD81 could offer new treatment strategies for LUSC.
More Related Videos
11:28Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
07:43Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018