Reconstructing the immunosenescence core pathway reveals global characteristics in pan-cancer

by Selleckchem | Nov 20 2023

Immunosenescence has been demonstrated to play an important role in tumor progression. However, there is lacking comprehensive analyses of immunosenescence-related pathways. Meanwhile, the sex disparities of immunosenescence in cancer are still poorly understood. In this study, we analyzed the multi-omics data of 12,836 tumor samples, including genomics, transcriptomics, epigenomics, proteomics, and metabolomics. We systematically identified immunosenescence pathways that were disordered across cancer types. The mutations and copy number variations of immunosenescence pathways were found to be more active in pan-cancer. We reconstructed the immunosenescence core pathways (ISC-pathways) to improve the ability of prognostic stratification in 33 cancer types. We also found the head and neck squamous carcinoma (HNSC) contained abundant sex-specific immunosenescence features and showed sex differences in survival. We found that OSI-027 was a potential sex-specific drug in HNSC tumors, which tended to be more effective in male HNSC by targeting the MTOR gene in the PI3K-Akt signaling pathway. In conclusion, our study provided a systematic understanding of immunosenescence pathways and revealed the global characteristics of immunosenescence in pan-cancer. We highlighted MTOR gene could be a powerful immunosenescence biomarker of HNSC that helps to develop sex-specific immunosenescence drugs.

Comments:

Your study appears to provide valuable insights into the role of immunosenescence in tumor progression, addressing gaps in current understanding. By analyzing multi-omics data from a large number of tumor samples, you were able to systematically identify and characterize immunosenescence pathways across various cancer types. The identification of immunosenescence core pathways (ISC-pathways) and their association with prognostic stratification in multiple cancer types is a significant contribution. Additionally, your study sheds light on the understudied area of sex disparities in immunosenescence and cancer.

The finding that immunosenescence pathways exhibit more activity in pan-cancer scenarios and the reconstruction of ISC-pathways for improved prognostic stratification are particularly noteworthy. Moreover, your observation of sex-specific immunosenescence features in head and neck squamous carcinoma (HNSC) and the identification of a potential sex-specific drug, OSI-027, targeting the MTOR gene in the PI3K-Akt signaling pathway, adds valuable information to the field.

The recognition of MTOR gene as a potential immunosenescence biomarker in HNSC could have significant implications for developing targeted therapies. Understanding the sex-specific differences in immunosenescence and their impact on cancer progression and survival can pave the way for personalized and more effective treatment strategies.

In summary, your study appears to be a comprehensive and important contribution to the understanding of immunosenescence pathways in cancer, highlighting their significance in tumor progression and prognosis, as well as addressing the need for sex-specific considerations in cancer research and treatment.