Machine learning-based transcriptome analysis of lipid metabolism biomarkers for the survival prediction in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a very high fatality rate. Our goal in this study is to find a reliable lipid metabolism-related signature associated with prognostic significance for HCC. In this study, HCC lipid metabolism-related molecular subtype analysis was conducted based on the 243 lipid metabolism genes collected from the Molecular Signatures Database. Several significant disparities in prognosis, clinicopathological characteristics, and immune and ferroptosis-related status were found across the three subtypes, especially between C1 and C3 subgroups. Differential expression analysis yielded 57 differentially expressed genes (DEGs) between C1 and C3 subtypes. GO and KEGG analysis was employed for functional annotation. Three of 21 prognostic DEGs (CXCL8, SLC10A1, and ADH4) were finally selected through machine-learning-based discovery and validation strategy. The risk score = (0.103) x expression value of CXCL8 + (-0.0333) x expression value of SLC10A1 + (-0.0812) x expression value of ADH4. We used these three to construct a HCC prognostic risk model, which stratified the patients of the validation cohort into two risk subtypes with significantly different overall survival. Our work provides possible significance of the lipid metabolism-associated model in stratifying patient prognosis and its feasibility to guide therapeutic selection.