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Pan-cancer transcriptomic analysis identified six classes of immunosenescence genes revealed molecular links between aging, immune system and cancer

Genes & Immunity volume 24, pages 81–91 (2023)Cite this article

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Abstract

Aging is a complex process that significantly impacts the immune system. The aging-related decline of the immune system, termed immunosenescence, can lead to disease development, including cancer. The perturbation of immunosenescence genes may characterize the associations between cancer and aging. However, the systematical characterization of immunosenescence genes in pan-cancer remains largely unexplored. In this study, we comprehensively investigated the expression of immunosenescence genes and their roles in 26 types of cancer. We developed an integrated computational pipeline to identify and characterize immunosenescence genes in cancer based on the expression profiles of immune genes and clinical information of patients. We identified 2218 immunosenescence genes that were significantly dysregulated in a wide variety of cancers. These immunosenescence genes were divided into six categories based on their relationships with aging. Besides, we assessed the importance of immunosenescence genes in clinical prognosis and identified 1327 genes serving as prognostic markers in cancers. BTN3A1, BTN3A2, CTSD, CYTIP, HIF1AN, and RASGRP1 were associated with ICB immunotherapy response and served as prognostic factors after ICB immunotherapy in melanoma. Collectively, our results furthered the understanding of the relationship between immunosenescence and cancer and provided insights into immunotherapy for patients.

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Fig. 1: Identification of immunosenescence gene across cancer types.
Fig. 2: Pan-cancer immunosenescence genes.
Fig. 3: Immunosenescence characteristics of cellular senescence signature genes.
Fig. 4: Clinical associations of immunosenescence genes across cancer types.
Fig. 5: Immunosenescence genes are associated with important functions.
Fig. 6: Somatic mutations of pan-cancer immunosenescence genes.
Fig. 7: Construction of immunosenescence signature of melanoma.

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Data availability

The datasets supporting the conclusions of this article are available in the TCGA repository, (https://tcga-data.nci.nih.gov/) and the GTEx portal (https://gtexportal.org).

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Acknowledgements

The authors gratefully thank the TCGA Research Network data repository for providing data for this work.

Funding

This work was supported by the National Natural Science Foundation of China [32070672], Heilongjiang Welfare Fund Organization of disabled Persons [HJ2022-1], and Post doctoral Science Foundation of Heilongjiang Province (LBH-Z19076).

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Authors and Affiliations

  1. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China

    Xinyue Wang, Shuang Guo, Hanxiao Zhou, Yue Sun, Jing Gan, Yakun Zhang, Wen Zheng, Caiyu Zhang, Peng Wang, Hui Zhi, Yue Gao & Shangwei Ning

  2. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150081, China

    Xiaofeng Chen

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  1. Xinyue Wang
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Contributions

XFC, SWN and XYW designed the study and performed analysis. SWN and HZ supervised the research and provided critical advice on the study. XYW, SG, PW, HXZ, YS, JG, CYZ and WZ collected data and developed the methodology. SWN and XYW wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiaofeng Chen or Shangwei Ning.

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Wang, X., Guo, S., Zhou, H. et al. Pan-cancer transcriptomic analysis identified six classes of immunosenescence genes revealed molecular links between aging, immune system and cancer. Genes Immun 24, 81–91 (2023). https://doi.org/10.1038/s41435-023-00197-9

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