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CDKN2 expression is a potential biomarker for T cell exhaustion in hepatocellular carcinoma
Shibo Wei 1 (Graduate student), Yan Zhang 2 (Graduate student), Baeki E. Kang 3 (Graduate student), Wonyoung Park 4 (Research worker), He Guo 5 (Research worker), Seungyoon Nam 6 (Professor), Jong-Sun Kang 2 (Professor), Jee-Heon Jeong 1 (Professor), Yunju Jo 7 (Research worker), Dongryeol Ryu 7,# (Professor), Yikun Jiang 8,# (Professor), Ki-Tae Ha 4,*,# (Professor)
1Department of Precision Medicine and 2Department of Molecular Cell Biology and 3Department of Physiology, Sungkyunkwan University School of Medicine,
4Department of Korean Medical Science, School of Korean Medicine, Pusan National University,
5Department of Obstetrics and Gynecology, The Second Hospital of Jilin University,
6Department of Genome Medicine and Science, Gachon University College of Medicine,
7Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology,
8Department of Orthopedics, The Second Hospital of Jilin University
Abstract
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.
Abstract, Accepted Manuscript [Submitted on November 13, 2023, Accepted on December 8, 2023]
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