Research Paper Volume 15, Issue 6 pp 2136—2157
The cell senescence regulator p16 is a promising cancer prognostic and immune check-point inhibitor (ICI) therapy biomarker
- 1 Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
- 2 Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang 330006, Jiangxi, P.R. China
- 3 Institute of Neuroscience, Nanchang University, Nanchang 330006, Jiangxi, P.R. China
- 4 JXHC Key Laboratory of Neurological Medicine, Nanchang 330006, Jiangxi, P.R. China
- 5 The Second Clinical Medical College of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
- 6 Department of Medical Ultrasonics, Integrated Chinese and Western Medicine Hospital of Jiangxi Province, Nanchang 330006, Jiangxi, P.R. China
- 7 The HuanKui Medical College of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
Received: January 8, 2023 Accepted: March 1, 2023 Published: March 23, 2023
https://doi.org/10.18632/aging.204601How to Cite
Copyright: © 2023 Tu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cyclin-dependent kinase inhibitor 2A (CDKN2A) encodes the cell senescence regulator protein p16. The expression of p16 raises in cell senescence and has a nuclear regulation in cell aging. Meanwhile, it's also reported to inhibit the aggression of several cancers. But its clinical application and role in cancer immunotherapy needs further investigation. We collected the transcriptional data of pan-cancer and normal human tissues from The Cancer Genome Atlas and the Genotype-Tissue Expression databases. CBioPortal webtool was employed to mine the genomic alteration status of CDKN2A across cancers. Kaplan-Meier method and univariate Cox regression were performed for prognostic assessments across cancers, respectively. Gene Set Enrichment Analysis is the main method used to search the associated cancer hallmarks associated with CDKN2A. TIMER2.0 was used to analyze the immune cell infiltration relevance with CDKN2A in pan-cancer. The associations between CDKN2A and immunotherapy biomarkers or regulators were performed by spearman correlation analysis. We found CDKN2A is overexpressed in most cancers and exhibits prognosis predictive ability in various cancers. In addition, it is significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations and immunoregulators. The most interesting finding is that CDKN2A can significantly predict anti-PDL1 therapy response. Finally, specific inhibitors which correlated with CDKN2A expression in different cancer types were also screened by using Connectivity Map (CMap) tool. The results revealed that CDKN2A acts as a robust cancer prognostic and immunotherapy biomarker. Its function in the regulation of cancer cell senescence might shape the tumor microenvironment and contribute to its predictive ability of immunotherapy.