Construction and validation of a fatty acid metabolism-related gene signature for predicting prognosis and therapeutic response in patients with prostate cancer.

Abstract

Reprogramming of fatty acid metabolism is a newly-identified hallmark of malignancy. However, no studies have systematically investigated the fatty acid metabolism related-gene set in prostate cancer (PCa). A cohort of 381 patients with gene expression and clinical data from The Cancer Genome Atlas was used as the training set, while another cohort of 90 patients with PCa from GEO (GSE70769) was used as the validation set. Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score. Associations between the risk score and clinical characteristics, immune cell infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) score, and response to chemotherapy were analyzed. Finally, the expression level of genes included in the model was validated using real-time PCR. A prognostic risk model based on five fatty acid metabolism related genes (ALDH1A1, CPT1B, CA2, CROT, and NUDT19) were constructed. Tumors with higher risk score were associated with larger tumor size, lymph node involvement, higher Gleason score, and poorer biochemical recurrence (BCR)-free survival. Furthermore, the high- and low-risk tumors exhibited distinct immune cell infiltration features and immune-related pathway activation. High-risk tumors were associated with favorable response to immunotherapy as indicated by high TMB and low TIDE score, but poor response to bicalutamide and docetaxel chemotherapy. This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.