A TMEFF2-regulated cell cycle derived gene signature is prognostic of recurrence risk in prostate cancer

• Published in: BMC cancer 2019-05, Vol.19 (1), p.423-423, Article 423
• Main Authors: Georgescu, Constantin, Corbin, Joshua M, Thibivilliers, Sandra, Webb, Zachary D, Zhao, Yan D, Koster, Jan, Fung, Kar-Ming, Asch, Adam S, Wren, Jonathan D, Ruiz-Echevarría, Maria J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Androgens; Biochemistry; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer genetics; Cancer surgery; Care and treatment; Cell cycle; Cell Cycle - genetics; Cell cycle genes; Cell Line, Tumor; Datasets; Datasets as Topic; Disease; Disease Progression; Disease-Free Survival; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genomics; Healthcare industry software; Humans; Male; Medical prognosis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Messenger RNA; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - surgery; Predictive Value of Tests; Prognosis; Prognostic markers; Prostate - pathology; Prostate - surgery; Prostate cancer; Prostatectomy; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - surgery; Proteins; Recurrence (Disease); Regression analysis; Retrospective Studies; Risk factorsS; Risk stratification; RNA; RNA interference; RNA, Messenger - metabolism; RNA-mediated interference; Studies; Surgery; Survival analysis; TMEFF2; Transcriptome; Tumor suppressor genes; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5592-6

The clinical behavior of prostate cancer (PCa) is variable, and while the majority of cases remain indolent, 10% of patients progress to deadly forms of the disease. Current clinical predictors used at the time of diagnosis have limitations to accurately establish progression risk. Here we describe the development of a tumor suppressor regulated, cell-cycle gene expression based prognostic signature for PCa, and validate its independent contribution to risk stratification in several radical prostatectomy (RP) patient cohorts. We used RNA interference experiments in PCa cell lines to identify a gene expression based gene signature associated with Tmeff2, an androgen regulated, tumor suppressor gene whose expression shows remarkable heterogeneity in PCa. Gene expression was confirmed by qRT-PCR. Correlation of the signature with disease outcome (time to recurrence) was retrospectively evaluated in four geographically different cohorts of patients that underwent RP (834 samples), using multivariate logistical regression analysis. Multivariate analyses were adjusted for standard clinicopathological variables. Performance of the signature was compared to previously described gene expression based signatures using the SigCheck software. Low levels of TMEFF2 mRNA significantly (p