RUNX3 methylation as a predictor for disease progression in patients with non-muscle-invasive bladder cancer.
OBJECTIVE
We have previously reported that RUNX3 inactivation by promoter hypermethylation correlated with advanced disease and poor clinical outcome in bladder cancer. In this study, we examined primary tumors from non-muscle-invasive bladder cancer (NMIBC) patients in order to investigate the relationship between RUNX3 methylation and disease progression.


METHODS
The association between the hypermethylation of RUNX3 and clinicopathological characteristics of 186 NMIBC samples was analyzed using methylation-specific polymerase chain reaction (MS-PCR).


RESULTS
RUNX3 methylation was associated with increased tumor stage, grade, and number of tumors (each P < 0.05). Kaplan-Meier estimates revealed significant differences in time to recurrence and progression based on RUNX3 methylation status (P = 0.043 and 0.006, respectively). RUNX3 methylation was an independent predictor of NMIBC progression on univariate and multivariate analysis. Combining tumor grade and RUNX3 methylation status demonstrated that patients with G3 tumors with RUNX3 methylation had a worse progression-free survival compared with the patients with lower-grade or unmethylated tumors [hazard ratio (HR), 19.450].


CONCLUSIONS
RUNX3 methylation status predicted the risk of NMIBC progression independently of tumor stage. In conjunction with tumor grade, RUNX3 methylation status in patients with NMIBC strongly predicts disease progression.
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
Chunri
C
Yan
Young-Won
YW
Kim
Yun-Sok
YS
Ha
Isaac Yi
IY
Kim
Yong-June
YJ
Kim
Seok-Joong
SJ
Yun
Sung-Kwon
SK
Moon
Suk-Chul
SC
Bae
Wun-Jae
WJ
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002648:Child; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
D050677:Core Binding Factor Alpha 3 Subunit; D004273:DNA, Neoplasm; C493729:Runx3 protein, human