Machine learning approach identifies inflammatory gene signature for predicting survival outcomes in hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, often linked to chronic inflammation. Our study aimed to probe inflammation pathways at the genetic level and pinpoint biomarkers linked to HCC patient survival. Methods We analyzed gene transcriptome data from 246 resectable stage I and II HCC patients from The Cancer Genome Atlas (TCGA). After selecting 917 inflammation-related genes (IRGs), we identified 104 differentially expressed genes (DEGs) through differential expression analysis. Two significant prognostic DEGs, S100A9 and PBK, were identified using LASSO and Cox regression, forming the basis of a risk score model. We conducted functional enrichment and immune landscape analyses, validated our findings on 170 patients from the GSE14520 dataset, and performed mutational analysis using TCGA somatic mutation data. Results We analyzed 296 samples (246 HCC, 50 normal liver), showing significant survival differences between high and low-risk groups based on our risk score model. Functional enrichment analysis unveiled inflammation-associated pathways. Validation using the GSE14520 dataset confirmed our risk score’s predictive ability, and we explored clinical correlations. Conclusion Our study delineates inflammation-related genomic changes in HCC, unveiling prognostic biomarkers with potential therapeutic implications. These findings deepen our understanding of HCC molecular mechanisms and may guide personalized therapeutic approaches, ultimately improving patient outcomes.