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Discovery of differentially expressed proteins for CAR-T therapy of ovarian cancers with a bioinformatics analysis
Dito Anurogo1,2, Chao-Lien Liu3,4, Yu-Chu Chang1
1International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Abstract:
Target antigens are crucial for developing chimeric antigen receptor (CAR)-T cells, but their application to ovarian cancers is limited. This study aimed to identify potential genes as CAR-T-cell antigen candidates for ovarian cancers. A differential gene expression analysis was performed on ovarian cancer samples from four datasets obtained from the GEO datasets. Functional annotation, pathway analysis, protein localization, and gene expression analysis were conducted using various datasets and tools. An oncogenicity analysis and network analysis were also performed. In total, 153 differentially expressed genes were identified in ovarian cancer samples, with 60 differentially expressed genes expressing plasma membrane proteins suitable for CAR-T-cell antigens. Among them, 21 plasma membrane proteins were predicted to be oncogenes in ovarian cancers, with nine proteins playing crucial roles in the network. Key genes identified in the oncogenic pathways of ovarian cancers included MUC1, CXCR4, EPCAM, RACGAP1, UBE2C, PRAME, SORT1, JUP, and CLDN3, suggesting them as recommended antigens for CAR-T-cell therapy for ovarian cancers. This study sheds light on potential targets for immunotherapy in ovarian cancers.
Insights
This study identifies key genes, including MUC1 and CXCR4, as potential targets for chimeric antigen receptor (CAR)-T cell therapy in ovarian cancers. These findings offer new avenues for ovarian cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Chimeric antigen receptor (CAR)-T cell therapy shows promise but faces limitations in ovarian cancer due to a lack of suitable target antigens.
- Identifying specific cell surface targets is critical for advancing CAR-T cell applications in ovarian malignancies.
Purpose of the Study:
- To identify and validate novel gene candidates for CAR-T cell therapy targeting ovarian cancers.
- To analyze differentially expressed genes, their oncogenic potential, and network roles in ovarian cancer.
Main Methods:
- Differential gene expression analysis of ovarian cancer datasets (GEO).
- Functional annotation, pathway and protein localization analysis.
- Oncogenicity and network analyses were performed on identified genes.
Main Results:
- 153 differentially expressed genes were identified in ovarian cancer samples.
- 60 genes encoding plasma membrane proteins were suitable for CAR-T cell targeting.
- Nine key oncogenic genes, including MUC1, CXCR4, and EPCAM, were highlighted as crucial targets.
Conclusions:
- MUC1, CXCR4, EPCAM, RACGAP1, UBE2C, PRAME, SORT1, JUP, and CLDN3 are recommended as potential antigens for ovarian cancer CAR-T cell therapy.
- This research provides a foundation for developing targeted immunotherapies for ovarian cancers.
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