Journal
COMPUTERS IN BIOLOGY AND MEDICINE
Volume 158, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.compbiomed.2023.106872
Keywords
Natural killer cell; Immune heterogeneity; Prognosis; Therapeutic response; Hepatocellular carcinoma
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This study identified 80 prognosis-related natural killer (NK) cell marker genes (NKGs) using single-cell RNA-sequencing analysis, and categorized hepatocellular carcinoma (HCC) patients into two subtypes based on these genes. A five-gene prognostic signature-NKscore (UBB, CIRBP, GZMH, NUDC, and NCL) was established, and differences in mutation status and immunotherapy sensitivity between the two NKscore risk groups were revealed. These findings provide a novel NK cell-related signature for predicting prognosis and immunotherapy efficacy in HCC patients.
Belonging to type 1 innate lymphoid cells (ILC1), natural killer (NK) cells play an important role not only in fighting microbial infections but also in anti-tumor response. Hepatocellular carcinoma (HCC) represents an inflammation-related malignancy and NK cells are enriched in the liver, making them an essential component of the HCC immune microenvironment. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis to identify the NK cell marker genes (NKGs) and uncovered 80 prognosis-related ones by the TCGA-LIHC dataset. Based on prognostic NKGs, HCC patients were categorized into two subtypes with distinct clinical outcomes. Subsequently, we conducted LASSO-COX and stepwise regression analysis on prognostic NKGs to establish a five-gene (UBB, CIRBP, GZMH, NUDC, and NCL) prognostic signature-NKscore. Different mutation statuses of the two risk groups stratified by NKscore were comprehensively characterized. Besides, the established NKscore-integrated nomogram presented enhanced predictive performance. Single sample gene set enrichment analysis (ssGSEA) analysis was used to uncover the landscape of the tumor immune microenvironment (TIME) and the high-NKscore risk group was characterized with an immune-exhausted phenotype while the low-NKscore risk group held relatively strong anti-cancer immunity. T cell receptor (TCR) repertoire, tumor inflammation signature (TIS), and Immunophenoscore (IPS) analyses revealed differences in immunotherapy sensitivity between the two NKscore risk groups. Taken together, we developed a novel NK cell-related signature to predict the prognosis and immunotherapy efficacy for HCC patients.
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