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12 November 2017 : Laboratory Research  

Promoter Methylation of RASSF1A indicates Prognosis for Patients with Stage II and III Colorectal Cancer Treated with Oxaliplatin-Based Chemotherapy

Xicai Sun1ABC, Wei Yuan2CD, Furong Hao2DE, Wenzhen Zhuang3FG

DOI: 10.12659/MSM.903927

Med Sci Monit 2017; 23:5389-5395

Abstract

BACKGROUND: The purpose of this study was to investigate the prognostic significance of methylation of RAS association domain family protein 1 (RASSF1A) in the promoter region for patients with stage II and III colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy.

MATERIAL AND METHODS: There were 108 eligible CRC patients and 78 healthy controls included in this study. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of RASSF1A in patients before and after chemotherapy. The effects of RASSF1A methylation on chemotherapy-sensitivity and prognosis for patients were also evaluated in the present study.

RESULTS: The frequency of RASSF1A methylation was higher in CRC patients than in the healthy controls (48.44% versus 5.13%, p<0.001). After two cycles of chemotherapy, methylation ratio was significantly decreased (21.30%, p<0.001). Promoter methylation of RASSF1A was significantly correlated with tumor stage and pathological differentiation (p=0.008 and p=0.007, respectively). Patients without methylation had a favorable objective response (OR), compared with those with methylation (53.33% versus 25%, p=0.014). Methylation status of RASSF1A could influence progression-free survival and overall survival (log rank test, p<0.05). Cox regression analysis indicated that RASSF1A methylation (HR=2.471, 95% CI=1.125–5.428, p=0.024) and OR (HR=2.678, 95% CI=1.085–6.610, p 0.033) were independently correlated with prognosis for patients treated with oxaliplatin-based chemotherapy.

CONCLUSIONS: Promoter methylation of RASSF1A can influence sensitivity to oxaliplatin-based chemotherapy, which can be used to predict outcomes for patients with stage II and III CRC. In addition, the aberrant methylation may be a promising target for improving chemotherapy efficacy.

Keywords: Chemoradiotherapy, Adjuvant, Colorectal Neoplasms, Methylation, Prognosis

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416