CDKN2A as a prognostic and diagnostic marker is a possible key contributor in hepatocellular carcinoma

Jun Ding; Ya-Ting Deng; Yi Deng; Ke-Ying Chen; Peng Guo; Fei Han

doi:10.21037/tcr-24-1845

CDKN2A as a prognostic and diagnostic marker is a possible key contributor in hepatocellular carcinoma

Transl Cancer Res. 2025 Apr 30;14(4):2303-2318. doi: 10.21037/tcr-24-1845. Epub 2025 Apr 15.

Authors

Jun Ding^#¹, Ya-Ting Deng^#^{2

3}, Yi Deng¹, Ke-Ying Chen^{2

3}, Peng Guo¹, Fei Han^{2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Department of Toxicology, School of Public Health, Chongqing Medical University, Chongqing, China.
³ Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing, China.

^# Contributed equally.

Abstract

Background: Hepatocellular carcinoma (HCC) represents one of the deadliest cancers with a rising incidence worldwide. Although the treatment of HCC has made some breakthroughs, the incidence and mortality of HCC are still increasing. The major cause for this is the lack of early diagnostic markers and effective therapeutic targets. This study aimed at identifying new diagnostic and therapeutic candidates, and determining the expression characteristic, clinical relevance, prognostic significance, diagnostic value and expression regulation of cyclin-dependent kinase inhibitor 2A (CDKN2A) in HCC.

Methods: Whole transcriptome sequencing data of normal and HCC tissues were used to screen and identify the diagnostic and therapeutic candidates. Tumor Immune Estimation Resource (TIMER) 2.0, University of California Santa Cruz (UCSC) Xena, Kaplan-Meier, immunohistochemical (IHC) analysis of tissue microarray, ESTIMATE, LinkedOmics, STRING and GeneMANIA were used to analyze the associations of CDKN2A expression with clinicopathological indices and tumor immune microenvironment, and determine the prognostic significance, diagnostic value, and possible expression regulation of CDKN2A.

Results: CDKN2A expression was significantly increased in HCC tissues, and closely correlated with patients' tumor size and clinical stage. High expression of CDKN2A was closely associated with poor prognosis and tumor microenvironment of HCC patients. CDKN2A expression has a clear diagnostic value for HCC. The up-regulation of CDKN2A in HCC may be related to the methylation of its promoter region. The enrichment analyses of CDKN2A co-expressed genes and interacting proteins revealed that CDKN2A likely promoted HCC progression through involvement of cell cycle regulation.

Conclusions: CDKN2A may serve as a new and promising prognostic and diagnostic marker, and an important therapeutic target in HCC.

Keywords: Hepatocellular carcinoma (HCC); diagnosis; expression regulation; immune microenvironment; prognosis.