Identification and validation of a lipid metabolism gene signature for predicting biochemical recurrence of prostate cancer after radical prostatectomy

Abstract

BackgroundPro5state cancer is one of the most commonly diagnosed cancers in men worldwide and biochemical recurrence occurs in approximately 25% of patients after radical prostatectomy. Current decisions regarding biochemical recurrence after radical prostatectomy are largely dependent on clinicopathological parameters, which are less accurate. A growing body of research suggests that lipid metabolism influences tumor development and treatment, and that prostate cancer is not only a malignancy but also a lipid metabolism disease. Therefore, this study aimed to identify the prognostic value of lipid metabolism-related gene signaling disease to better predict biochemical recurrence and contribute to clinical decision-making.MethodsExpression data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) database and the MSKCC database. Candidate modules closely associated with BCR were screened by univariate and LASSOcox regression analyses, and multivariate Cox regression analyses were performed to construct gene signatures. Kaplan-Meier (KM) survival analysis, time-dependent subject operating curves (ROC), independent prognostic analysis, and Nomogram were also used to assess the prognostic value of the signatures. In addition, Gene Ontology Analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore potential biological pathways.ResultsA 6-gene lipid metabolism-related gene signature was successfully constructed and validated to predict biochemical recurrence in prostate cancer patients. In addition, we identified the 6-gene signature as an independent risk factor. Functional analysis showed that lipid metabolism-related genes were closely associated with arachidonic acid metabolism, PPAR transduction signaling pathway, fatty acid metabolism, peroxisome, and glycerophospholipid metabolism. Prognostic models were associated with immune cell infiltration.ConclusionWe have successfully developed a novel lipid metabolism-related gene signature that is highly effective in predicting BCR in patients with limited prostate cancer after RP and created a prognostic Nomogram. Furthermore, the signature may help clinicians to select high-risk subpopulations, predict patient survival, and facilitate more personalized treatment than traditional clinical factors.