Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma

BACKGROUND: Despite significant advances in multimodality treatments, hepatocellular carcinoma (HCC) remains one of the most common malignant tumors. Identification of novel prognostic biomarkers and molecular targets is urgently needed. AIM: To identify potential key genes associated with tumor microenvironments and the prognosis of HCC. METHODS: The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of HCC. These genes were validated in four independent HCC cohorts. Survival-related key genes were identified by a LASSO Cox regression model. RESULTS: HCC patients with a high immune/stromal score had better survival benefits than patients with a low score. A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices, 147 of which were associated with overall survival. Subsequently, 52 of 147 survival-related DEGs were validated in additional cohorts. Finally, ten key genes (STSL2, TMC5, DOK5, RASGRP2, NLRC3, KLRB1, CD5L, CFHR3, ADH1C, and UGT2B15) were selected and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival. CONCLUSION: This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC, thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.