Abstract
Neoadjuvant chemoradiotherapy (nCRT) is widely used to treat patients with locally advanced rectal cancer (LARC), and treatment responses vary. Fatty acid metabolism (FAM) is closely associated with carcinogenesis and cancer progression. In this study, we investigated the vital role of FAM on the gut microbiome and metabolism in the context of cancer. We screened 34 disease-free survival (DFS)-related, FAM-related, and radiosensitivity-related genes based on the Gene Expression Omnibus database. Subsequently, we developed a five-gene FAM-related signature using the least absolute shrinkage and selection operator Cox regression model. The FAM-related signature was also validated in external validation from Fujian Cancer Hospital for predicting nCRT response, DFS, and overall survival (OS). Notably, patients with a low-risk score were associated with pathological complete response and better DFS and OS outcomes. A comprehensive evaluation of the tumor microenvironment based on the FAM-related signature revealed that patients with high-risk scores were closely associated with activating type I interferon response and inflammation-promoting functions. In conclusion, our findings indicate the potential ability of FAM to predict nCRT response and the prognosis of DFS and OS in patients with LARC.