Combined analysis of CRMP4 methylation levels and CAPRA-S score predicts metastasis and outcomes in prostate cancer patients

Abstract

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34–19.80) and 12.83 (95% CI: 2.16–26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.

Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calcium‑mediated cell signaling

“…Among the genes significantly downregulated in radioresistant cell lines than in their parental cells, collapsin response mediator protein 4 (CRMP4) was further examined in the present study concerning the association between tumor growth and radioresistance. It is known that CRMPs influence various intracellular signal transduction pathways, including VEGF, RhoA, GSK3β, and Sema3A ( 29 , 30 ); moreover, CRMP4 is involved in neurodevelopmental disorders such as schizophrenia, neurological disorders such as Alzheimer's disease ( 31 ), and various types of cancers such as breast, prostate, gastric, and hepatocellular carcinomas ( 11 , 32 – 35 ).…”