A novel fatty acid metabolism-related gene signature predicts the prognosis, tumor immune properties, and immunotherapy response of colon adenocarcinoma patients

Abstract

Colon adenocarcinoma (COAD) has a high incidence and death rate. Despite the fact that change in fatty acid metabolism promotes tumor growth and metastasis to the greatest degree among metabolite profiles, a thorough investigation on the involvement of fatty acid metabolism-related genes (FAMRGs) in COAD has yet not been conducted. Here, the clinical data as well as the gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) database. Based on the FAMRG expression data and clinical information, a FAMRG risk signature was developed using LASSO as well as multivariate and univariate Cox regression analyses. Then, the nomogram was used to create a customized prognostic prediction model, and the calibration and receiver operating characteristic curves were used to evaluate the nomogram's prediction performance and discriminative capability. Lastly, a number of studies were conducted to assess the influence of independent FAMRGs on COAD, including unsupervised cluster analysis, functional analysis, and drug sensitivity analysis. Three hundred and sixty-seven patients were included in this study, and a 12-FAMRG risk signature was discovered in the training cohort based on a detailed examination of the FAMRGs expression data and clinical information. After that, risk scores were computed to classify patients into low or high-risk groups, and the Kaplan–Meier curve analysis revealed that patients in the low-risk group exhibited an elevated overall survival (OS) rate. The FAMRG was shown to be substantially correlated with prognosis in multivariate Cox regression analysis and was validated using the validation dataset. Then, using the clinical variables and risk signature, we developed and validated a prediction nomogram for OS. Functional characterization showed a strong correlation between this signature and immune cell infiltration and immune modulation. Additionally, by evaluating the GDSC database, it was determined that the high-risk group exhibited medication resistance to many chemotherapeutic and targeted medicines, including VX.680, gemcitabine, doxorubicin, and paclitaxel. Overall, we have revealed the significance of a FAMRG risk signature for predicting the prognosis and response to immunotherapy in COAD, and our findings might contribute to an enhanced comprehension of metabolic pathways and the future development of innovative COAD therapeutic methods.