Aberrant Methylation of CDH13 is a Potential Biomarker for Predicting the Recurrence and Progression of Non Muscle Invasive Bladder Cancer

Abstract

BackgroundCDH13 is a novel tumor suppressor gene often inactivated by aberrant promoter methylation in human cancers. Previous studies have shown that CDH13 methylation correlated with advanced disease and poor prognosis in non-muscle invasive bladder cancer (NMIBC). The aim of the current study was to investigate the correlations between CDH13 methylation and disease recurrence as well as progression of NMIBC.Material/MethodsThe methylation status of CDH13 in 178 NMIBC samples and 38 normal bladder epithelial tissues was examined by methylation-specific PCR (MSP), and then correlated with clinicopathological features.ResultsWe found that CDH13 methylation occurs frequently in NMIBC, and significantly correlates with high grade, advanced stage, larger tumor size, and tumor recurrence and progression. Moreover, patients with methylated CDH13 exhibited significantly shorter recurrence-free survival (P<0.0001) and progression-free survival (P=0.0060) than patients with unmethylated CDH13. In addition, a multivariate Cox proportional hazard model analysis suggests that CDH13 methylation is an independent predictor for the recurrence (P=0.0043) and progression (P=0.0016) of NMIBC after initial transurethral resection.ConclusionsOur findings demonstrate that CDH13 methylation is a frequent event in NMIBC, and is associated with unfavorable tumor features. It should be used as an independent predictor for the recurrence and progression of NMIBC, and may be useful for the design of individualized therapeutic modalities.

Identification of γ-Synuclein as a Stage-Specific Marker in Bladder Cancer by Immunohistochemistry

“…SNCG has been reported to have a strong connection with malignancies such as breast, gastric, pancreatic, esophagus, colon, and prostate cancers [ 13 – 18 ]. Many genes, including SNCG, are involved in DNA methylation, which plays an important role in the occurrence and development of tumors [ 19 – 21 ]. Furthermore, SNCG is also involved in resistance to certain chemotherapeutic or antimicrotubule agents in breast cancer treatment [ 22 ].…”

Up-Regulation of miR-9 Target CBX7 to Regulate Invasion Ability of Bladder Transitional Cell Carcinoma

“…Surgical resection is still the most effective therapy for non-invasive TCC patients. Although chemotherapy based on BCG may reduce recurrence in patients, approximately 70% will recur and 25±30% will eventually progress to muscle invasive disease or distant metastasis [ 4 , 5 ]. Thus, there is an urgent need to find new therapeutic targets and strategies, which may be helpful in understanding the molecular mechanisms and improving TCC therapy.…”

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

“…Finally, all of the Portuguese studies were conducted by Dr. Carmen Jerónimo's group in IPO (Portuguese Oncology Institute) [32][33][34][35][36]. Regarding Asian studies, significant contributions have been made by Dr. Ying-Li Lin [37][38][39][40][41][42][43] at Jiangsu University and Dr. Liqun Zhou (especially in UTUC studies) [44][45][46]…”

“…The studies by Dr. Lin at JU have reported that methylation of CDH13 is associated with increased recurrence risk (p=0.0043), shorter time to progression (p=0.006), lower RFS (p<0.0001) [43] and with an increased risk of death (p=0.0071) [41]. In another of his studies, CDH11 methylation correlated with poor OS (p=0.0004) [40].…”