Clinical Implications and Prognostic Values ofProstate Cancer Susceptibility CandidateMethylation in Primary Nonmuscle Invasive Bladder Cancer

Abstract

DNA methylation is the most common and well-characterized epigenetic change in human cancer. Recently, an association between prostate cancer susceptibility candidate (PRAC) methylation and genitourinary cancer was proposed. The aim of the present study was to evaluate the association between PRAC methylation status and clinicopathological parameters and prognosis in long-term follow-up primary nonmuscle invasive bladder cancer (NMIBC). The clinical relevance of PRAC methylation was determined in 136 human bladder specimens (eight normal controls [NCs] and 128 primary NMIBCs) using quantitative pyrosequencing analysis. PRAC methylation was significantly higher in NMIBC patients than in NCs and was significantly associated with higher grade and more advanced stage of cancer. Kaplan-Meier estimates revealed significant difference in tumor recurrence and progression according to PRAC methylation status (both p < 0.05). Multivariate Cox regression analysis revealed that the PRAC methylation status was a strong predictor of recurrence (hazard ratio [HR], 2.652; p = 0.012) and progression (HR, 9.531; p = 0.035) of NMIBC. Enhanced methylation status of PRAC was positively associated with a high rate of recurrence and progression in NMIBC patients, suggesting that PRAC methylation may be a promising prognostic marker of NMIBC.

Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution

“…Of note, KRT13 plays a directive role in prostate cancer metastasis and its expression in primary prostate tumors is predictive of metastasis and lower survival (Li et al, 2016). Little is known about PRAC1 , which encodes a small nuclear protein in human prostate and bladder cancer with prognostic capability (Kim et al, 2015; Lenka et al, 2013). That KRT13 and PRAC1 are high in normal prostate stem cells and re-expressed in prostate cancers supports the emerging concept that during cancer progression, epithelia transition to a stem-like state that permits their robust growth potential.…”

Low expression of protocadherin7 (PCDH7) is a potential prognostic biomarker for primary non-muscle invasive bladder cancer

“…Patients with intermediate or high risk NMIBC were given one cycle of intravesical instillation therapy, and all the patients were followed up and managed according to standard guidelines [ 27 , 28 ]. Recurrence was defined as the return of NMIBC at a lower or equivalent pathologic stage, and progression was defined as muscle invasion or lymph node/distant metastatic disease [ 29 ].…”

The prognostic role of epigenetic dysregulation in bladder cancer: A systematic review

“…However, VHL methylation was not prognostic in a similar Japanese NMIBC cohort [60]. Methylation of PRAC independently predicted recurrence and progression (p=0.012 and p=0.035, respectively) in Korean NMIBC patients [53]. Also in NMIBC, methylation of ZIC4 has been found to predict poor PFS (p=0.037) [74].…”