CDKN2 expression is a potential biomarker for T cell exhaustion in hepatocellular carcinoma
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Hepatocellular Carcinoma (HCC), the predominant primaryhepatic malignancy, is the prime contributor to mortality. Despitethe availability of multiple surgical interventions, patientoutcomes remain suboptimal. Immunotherapies have emergedas effective strategies for HCC treatment with multiple clinicaladvantages. However, their curative efficacy is not always satisfactory,limited by the dysfunctional T cell status. Thus, thereis a pressing need to discover novel potential biomarkers indicativeof T cell exhaustion (Tex) for personalized immunotherapies. One promising target is Cyclin-dependent kinaseinhibitor 2 (CDKN2) gene, a key cell cycle regulator with aberrantexpression in HCC. However, its specific involvementremains unclear. Herein, we assessed the potential of CDKN2expression as a promising biomarker for HCC progression,particularly for exhausted T cells. Our transcriptome analysisof CDKN2 in HCC revealed its significant role involving inHCC development. Remarkably, single-cell transcriptomic analysisrevealed a notable correlation between CDKN2 expression,particularly CDKN2A, and Tex markers, which was furthervalidated by a human cohort study using human HCC tissuemicroarray, highlighting CDKN2 expression as a potential biomarkerfor Tex within the intricate landscape of HCC progression. These findings provide novel perspectives that hold promisefor addressing the unmet therapeutic need within HCCtreatment.
Abstract
Hepatocellular Carcinoma (HCC), the predominant primaryhepatic malignancy, is the prime contributor to mortality. Despitethe availability of multiple surgical interventions, patientoutcomes remain suboptimal. Immunotherapies have emergedas effective strategies for HCC treatment with multiple clinicaladvantages. However, their curative efficacy is not always satisfactory,limited by the dysfunctional T cell status. Thus, thereis a pressing need to discover novel potential biomarkers indicativeof T cell exhaustion (Tex) for personalized immunotherapies. One promising target is Cyclin-dependent kinaseinhibitor 2 (CDKN2) gene, a key cell cycle regulator with aberrantexpression in HCC. However, its specific involvementremains unclear. Herein, we assessed the potential of CDKN2expression as a promising biomarker for HCC progression,particularly for exhausted T cells. Our transcriptome analysisof CDKN2 in HCC revealed its significant role involving inHCC development. Remarkably, single-cell transcriptomic analysisrevealed a notable correlation between CDKN2 expression,particularly CDKN2A, and Tex markers, which was furthervalidated by a human cohort study using human HCC tissuemicroarray, highlighting CDKN2 expression as a potential biomarkerfor Tex within the intricate landscape of HCC progression. These findings provide novel perspectives that hold promisefor addressing the unmet therapeutic need within HCCtreatment.
참고문헌 (31)
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