Fatty acid β-oxidation-associated prognostic model in gastric cancer and functional validation of IL-6 as a potential therapeutic target

Gastric cancer (GC) poses a significant health threat, and alterations in Fatty acid β-oxidation (FAO) may influence its progression. However, the precise mechanisms underlying this association remain unclear. FAO-related genes were analyzed using transcriptomic datasets from databases of GEO and TCGA. Totally 160 FAO-associated genes were identified, and a risk scoring model was subsequently established to stratify patients into groups of low- and high-risk. Immune characteristics, drug sensitivities, and hub genes, including IL-6, were assessed. Subsequently, immunoblotting and immunohistochemistry were performed on GC cell lines and tissue samples to evaluate IL-6 expression. Analysis of the TCGA and GEO databases revealed a FAO-related gene signature comprising ACADS, ACO2, CPT2, SLC22A5, AOC3, CD36, CIDEA, G0S2, GABARAPL1, and SERINC1. We also examined gene mutations and constructed a prognostic risk scoring model with validation achieved through a nomogram to predict gastric cancer risk. Immune infiltration analysis and drug sensitivity testing (e.g. AG-014699, Axitinib, BX-795, and Cisplatin) were also conducted. IL-6 emerged as a core gene with significant expression difference across cellular and tissue levels. FAO plays a critical role in the prognosis of GC, and IL-6 may serve as a key biomarker for diagnosis and therapeutic strategies.