OGT and FLAD1 Genes Had Significant Prognostic Roles in Progressive Pathogenesis in Prostate Cancer

Abstract

Purpose: This study aimed to identify metabolic genes associated with non-metastatic prostate cancer progression using The Cancer Genome Atlas (TCGA) datasets and validate their prognostic role by assessing patients’ immunohistochemical prostatectomy specimens. Materials and Methods: Several metabolic candidate genes analyzed were highly correlated with cancer progression to biochemical recurrence (BCR) and deaths in 335 patients’ genetic information from TCGA datasets. Those candidate genes and their expressions in tissue specimens were validated retrospectively by immunohistochemical analysis of radical prostatectomy specimens collected from 514 consecutive patients with non-metastatic prostate cancer between 2000 and 2015. The Cox proportional-hazards model was used to predict the prognostic role of each candidate gene expression in BCR and survival prognoses with a statistical significance of p-value <0.05. Twenty metabolic genes were identified by own developed software (Targa; https://github.com/cgab-ncc/TarGA), whose median expression levels consistently increased with cancer progression to the BCR and deaths. Results: Five metabolic genes (MAT2A, FLAD1, UGDH, OGT, and RRM2) were found to be significantly involved in the overall survival in the TCGA dataset. The immunohistochemical validation and clinicopathological data showed that OGT (hazard ratio [HR], 1.002; 95% confidence interval [CI], 1.001–1.003) and FLAD1 (HR, 1.010; 95% CI, 1.003–1.017) remained significant factors for BCR and cancer-specific survival, respectively, in the multivariate analysis even after adjusting for confounding clinicopathological parameters (p<0.05). Conclusions: OGT and FLAD1 showed significant prognostic factors of disease progression, even after adjustment for confounding clinicopathological parameters in non-metastatic prostate cancer.

Keywords

• big data
• metabolism
• prostate cancer
• tumor staging