Combined analysis of bulk and single-cell RNA sequencing reveals novel natural killer cell-related prognostic biomarkers for predicting immunotherapeutic response in hepatocellular carcinoma

INTRODUCTION: Natural killer (NK) cells play an irreplaceable and important role as a subtype of innate immune cells in the contemporary setting of antitumor immunity. METHODS: We chose a total of 1,196 samples for this analysis from the public dataset’s six separate cohorts. To identify 42 NK cell marker genes, we first carried out a thorough study of single-cell RNA sequencing data from the GSE149614 cohort of hepatocellular carcinoma (HCC). RESULTS: Using the NK cell marker genes in the TCGA cohort, we next created a seven-gene prognostic signature, separating the patients into two categories with distinct survival patterns. This signature’s prognostic prediction ability was well verified across several validation cohorts. Patients with high scores had higher TIDE scores but lower immune cell infiltration percentages. Importantly, low-scoring patients had superior immunotherapy response and prognosis than high-scoring patients in an independent immunotherapy cohort (IMvigor210). Finally, we used CD56 and TUBA1B antibodies for immunohistochemical labeling of HCC tissue sections, and we discovered a lower number of CD56+ cells in the HCC tissue sections with high TUBA1B expression. DISCUSSION: In summary, our research created a unique prognostic profile based on NK cell marker genes that may accurately predict how well immunotherapy would work for HCC patients.