Transcriptome Profiles Reveal a 12-Signature Metabolic Prediction Model and a Novel Role of Myo-Inositol Oxygenase in the Progression of Prostate Cancer.

Abstract

Prostate adenocarcinoma (PRAD) is an extremely common type of cancer in the urinary system. Here, we aimed to establish a metabolic signature to identify novel targets in a predictive model of PRAD patients. A total of 133 metabolic differentially expressed genes (MDEGs) were identified with significant prognostic value. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a 12-mRNA signature model, a metabolic prediction model (MPM), in 491 PRAD patients. The risk score of the MPM significantly predicted the progression of PRAD patients (p < 0.001, area under the curve (AUC) = 0.745). Furthermore, myo-inositol oxygenase (MIOX), the most prominently upregulated metabolic enzyme and hub gene in the protein–protein interaction network of the MPM, showed significant prognostic implications. Next, MIOX expression in normal prostate tissues was lower than in PRAD tissues, and high MIOX expression was significantly associated with disease progression (p = 0.005, HR = 2.274) in 81 PRAD patients undergoing first-line androgen receptor signaling inhibitor treatment from the Renji cohort. Additionally, MIOX was significantly involved in the abnormal immune infiltration of the tumor microenvironment and associated with the DNA damage repair process of PRAD. In conclusion, this study provides the first opportunity to comprehensively elucidate the landscape of prognostic MDEGs, establish novel prognostic modeling of MPM using large-scale PRAD transcriptomic data, and identify MIOX as a potential prognostic target in PRAD patients from multiple cohorts. These findings help manage risk assessment and provide valuable insights into treatment strategies for PRAD.