1. A new high-throughput screening methodology for the discovery of cancer-testis antigen using multi-omics data.
- Author
-
Li D, Xia L, Zhang X, Liu Y, Wang Z, Guo Q, Huang P, Leng W, and Qin S
- Subjects
- Humans, Male, Cell Line, Tumor, Testis metabolism, Gene Expression Regulation, Neoplastic, Genomics, Promoter Regions, Genetic, Sequence Analysis, RNA, Multiomics, Antigens, Neoplasm metabolism, Antigens, Neoplasm genetics, DNA Methylation, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, High-Throughput Screening Assays methods
- Abstract
Background: Cancer/testis antigens (CTAs), also known as tumor-specific antigens (TSAs) are specifically expressed in cancer cells and exhibit high immunogenicity, making them promising targets for immunotherapy and cancer vaccines., Methods: A new integrated high-throughput screening methodology for CTAs was proposed in this study through combining DNA methylation and RNA sequencing data. Briefly, the genes with increased transcript level and decreased DNA methylation were identified by multi-omics analysis. RNA sequencing studies in cell lines exposed to DNA methyltransferase (DNMT) inhibitors were performed to validate the inherent causal relationship between DNA hypomethylation and gene expression upregulation., Results: We proposed a new integrated high-throughput screening methodology for identification of CTAs using multi-omics analysis. In addition, we tested the feasibility of this method using gastric cancer (GC) as an example. In GC, we identified over 2000 primary candidate CTAs and ultimately identified 20 CTAs with significant tissue-specificity, including a testis-specific serine protease TESSP1/PRSS41. Integrated analysis confirmed that PRSS41 expression was reactivated in gastrointestinal cancers by promoter DNA hypomethylation at the CpG site (cg08104780). Additionally, DNA hypomethylation of PRSS41 predicted a poor prognosis in GC., Conclusion: We propose a new high-throughput screening method for the identification of CTAs in cancer and validate its effectiveness. Our work emphasizes that serine protease PRSS41 is a novel TSA that is reactivated in GC due to promoter DNA hypomethylation., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF