BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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CDKN2 expression is a potential biomarker for T cell exhaustion in hepatocellular carcinoma

  • Shibo Wei (Department of Precision Medicine, Sungkyunkwan University School of Medicine) ;
  • Yan Zhang (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Baeki E. Kang (Department of Physiology, Sungkyunkwan University School of Medicine) ;
  • Wonyoung Park (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • He Guo (Department of Obstetrics and Gynecology, The Second Hospital of Jilin University) ;
  • Seungyoon Nam (Department of Genome Medicine and Science, AI Convergence Center for Medical Science, Gachon University Gil Medical Center, Gachon University College of Medicine) ;
  • Jong-Sun Kang (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Jee-Heon Jeong (Department of Precision Medicine, Sungkyunkwan University School of Medicine) ;
  • Yunju Jo (Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology) ;
  • Dongryeol Ryu (Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology) ;
  • Yikun Jiang (Department of Orthopedics, The Second Hospital of Jilin University) ;
  • Ki-Tae Ha (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
  • 투고 : 2023.11.13
  • 심사 : 2023.12.08
  • 발행 : 2024.06.30
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초록

Hepatocellular Carcinoma (HCC), the predominant primary hepatic malignancy, is the prime contributor to mortality. Despite the availability of multiple surgical interventions, patient outcomes remain suboptimal. Immunotherapies have emerged as effective strategies for HCC treatment with multiple clinical advantages. However, their curative efficacy is not always satisfactory, limited by the dysfunctional T cell status. Thus, there is a pressing need to discover novel potential biomarkers indicative of T cell exhaustion (Tex) for personalized immunotherapies. One promising target is Cyclin-dependent kinase inhibitor 2 (CDKN2) gene, a key cell cycle regulator with aberrant expression in HCC. However, its specific involvement remains unclear. Herein, we assessed the potential of CDKN2 expression as a promising biomarker for HCC progression, particularly for exhausted T cells. Our transcriptome analysis of CDKN2 in HCC revealed its significant role involving in HCC development. Remarkably, single-cell transcriptomic analysis revealed a notable correlation between CDKN2 expression, particularly CDKN2A, and Tex markers, which was further validated by a human cohort study using human HCC tissue microarray, highlighting CDKN2 expression as a potential biomarker for Tex within the intricate landscape of HCC progression. These findings provide novel perspectives that hold promise for addressing the unmet therapeutic need within HCC treatment.

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과제정보

This study was performed according to the Declaration of Helsinki, and approved by the Ethics Committee of Shanghai Outdo Biotech Company (Protocol code: SHYJS-CP-1701002). The informed consent was obtained from all subjects involved in the study. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2022R1I1A1A01063460 and 2021R1A5A8029876 to Y.J.; 2023R1A2C3006220, 2022K2A9A1A06091879, and RS2023-00261370 to D.R. and K.T.H). Moreover, the study was also supported by an Inha University Research Grant to D.R. and a "GIST Research Institute (GRI) IIBR" grant funded by the GIST to D.R. in 2023.

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