Prostate cancer (PCa) is the second most common male cancer worldwide, but effective biomarkers for the presence or progression risk of disease are currently elusive. In a series of nine matched histologically confirmed PCa and benign samples, we carried out an integrated transcriptome-wide gene expression analysis, including differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), which identified a set of potential gene markers highly associated with tumour status (malignant vs. benign). We then used these genes to establish a minimal progression-free survival (PFS)-associated gene signature (GS) (PCBP1, PABPN1, PTPRF, DANCR, and MYC) using least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses from The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) dataset. Our signature was able to predict PFS over 1, 3, and 5 years in TCGA-PRAD dataset, with area under the curve (AUC) of 0.64-0.78, and our signature remained as a prognostic factor independent of age, Gleason score, and pathological T and N stages. A nomogram combining the signature and Gleason score demonstrated improved predictive capability for PFS (AUC: 0.71-0.85) and was superior to the Cambridge Prognostic Group (CPG) model alone and some conventionally used clinicopathological factors in predicting PFS. In conclusion, we have identified and validated a novel five-gene signature and established a nomogram that effectively predicted PFS in patients with PCa. Findings may improve current prognosis tools for PFS and contribute to clinical decision-making in PCa treatment.
Frontiers in oncology. 2022 Aug 12*** epublish ***
Zhuofan Mou, Jack Spencer, Bridget Knight, Joseph John, Paul McCullagh, John S McGrath, Lorna W Harries
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Devon, United Kingdom., Translational Research Exchange at Exeter, Living Systems Institute, University of Exeter, Exeter, United Kingdom., National Institute for Health and Care Research (NIHR) Exeter Clinical Research Facility, Royal Devon and Exeter National Health Service (NHS) Foundation Trust, Royal Devon and Exeter Hospital, Exeter, United Kingdom., Department of Pathology, Royal Devon and Exeter National Health Service (NHS) Foundation Trust, Exeter, United Kingdom.