Development and Clinical Validation of a Novel 5 Gene Signature Based on Fatty Acid Metabolism-Related Genes in Oral Squamous Cell Carcinoma.

ABSTRACT

Background/Aim: Lipid metabolism disorders play a crucial role in tumor development and progression. The aim of the study focused on constructing a novel prognostic model of oral squamous cell carcinoma (OSCC) patients using fatty acid metabolism-related genes. Methods: Microarray test and data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed genes related to fatty acid metabolism. The quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of targeted fatty acid metabolism genes. A risk predictive scoring model of fatty acid metabolism-related genes was generated using a multivariate Cox model. The efficacy of this model was assessed by time-dependent receiver operating characteristic curve (ROC). Results: 14 fatty acid metabolism-related genes were identified by microarray test and TCGA database analysis and then confirmed by PCR. Finally, a 5 gene signature (ACACB, FABP3, PDK4, PPARG, and PLIN5) was constructed and a RiskScore was calculated for each patient. Compared to the high RiskScore group, the low RiskScore group had better overall survival (OS) (p = 0.02). The RiskScore derived from a 5 gene signature was a prognostic factor (HR 3.73, 95% CI 1.38, 10.09) for OSCC patients. The predictive classification efficiencies of RiskScore were evaluated and the area under the curve (AUC) values for 1, 3, and 5 years were 0.613, 0.652, and 0.681, respectively. Then we compared the predictive performance of the prognostic model with or without the RiskScore. The 5 gene-derived RiskScore can improve the predictive performance with AUC values of 0.760, 0.803, and 0.830 for 1, 3, and 5 years OS in prognostic model including the RiskScore. While the predicted AUC values of the model without RiskScore for 1, 3, and 5 years OS were 0.699, 0.715, and 0.714, respectively. Conclusion: We developed a predictive score model using 5 fatty acid metabolism-related genes, which could be a potential prognostic indicator in OSCC.