Identification and Validation of an Inflammatory Response-Related Polygenic Risk Score as a Prognostic Marker in Hepatocellular Carcinoma

AIMS: We hypothesized that the expression patterns of inflammatory response-related genes may be a potential tool for hepatocellular carcinoma (HCC) risk scoring. BACKGROUND: Inflammatory response plays a pivotal role in the pathogenesis of HCC. OBJECTIVE: To establish and validate a hallmark inflammatory response gene-based polygenic risk score as a prognostic tool in HCC. METHODS: We screened differentially expressed inflammatory response genes and established an inflammatory response-related polygenic risk score (IRPRS) in an HCC-related dataset. Patients with HCC were categorized into high- and low-risk groups according to the median IRPRS, and the overall survival between the two groups was compared. The IRPRS was validated in an independent external dataset. Tumor-infiltrating lymphocytes (TILs) in high- and low-risk groups were compared, and gene set enrichment analysis was performed to characterize high-risk HCC identified using this IRPRS. RESULTS: Four differentially expressed hallmark inflammatory response genes (CD14, AQP9, SERPINE1, and ITGA5) were identified to construct the IRPRS. Patients in the high-risk group had significantly shorter overall survival than those in the low-risk group in both the training set and the test set. Furthermore, the IRPRS remained an independent prognostic factor compared to the routine clinicopathological characteristics. Many cancer-related hallmark gene sets and TILs were significantly enriched in the high-risk group. CONCLUSIONS: We established and validated a four-hallmark inflammatory response gene-based polygenic risk score, which could successfully divide patients with HCC into high-risk and low-risk groups. These two risk groups of HCC possess significantly distinct prognostic and biological characteristics.