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eISSN: 1643-3750

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

Xicai Sun, Wei Yuan, Furong Hao, Wenzhen Zhuang

(Department of Health Management, Weifang People’s Hospital, Weifang, Shandong, China (mainland))

Med Sci Monit 2017; 23:5389-5395

DOI: 10.12659/MSM.903927


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

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
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