Pan-Cancer Analysis Delineates Molecular Portraits of Cancer/Testis Antigen and Clinical Implications of the Cancer/Testis Antigen Score

This is the authors' abstract. We don't add key points for this paper.

Human cancer/testis antigens (CTAs) have a biased expression pattern in various human malignancies and normal tissues restricted to the testis and placenta. While im-munotherapies have shown promise across cancers, the roles of CTAs remain unclear. Here, we systematically, investigated the genetic alterations, methylation status, pathway modulation, drug sensitivity, and clinical relevance of key CTA genes across 33 cancer types. We proposed the calculation of the CTA score for each sample based on the gene set variation analysis (GSVA). We discovered that there were pervasive ge-netic modifications in the CTA genes. The classification system based on these CTA genes was verified to be beneficial for prognostic stratification in KIRC, GBM, and COAD. Additionally, we identified 9 key CTA genes that are prognostic factors and are differentially expressed in most cancer types. Target-driven reverse network pharmacology identified a CTA-centered herb–compound–target network linking the 9 key CTA genes to 20 compounds and 238 herbs, with CEP55 and OIP5 representing the most extensively connected nodes. Subsequently, CEP55 showed hypomethylation and an inverse correlation with its expression across multiple tumors. ODF2 downregulation in liver cancer was attributed to promoter hypermethylation, confirmed by methylation-specific PCR (MSP), reverse tran-scription PCR (RT-PCR) and bisulfite genomic sequencing. Moreover, the CTA score exhibited desirable per-formance in immune activity prediction and immune response assessment. Overall, this study offers a comprehensive molecular portrait of CTAs and highlights their clinical utility in cancer immunotherapy.