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CDX2基因启动子甲基化在预测结直肠癌治疗疗效中的作用

Methylation of CDX2 gene promoter in the prediction of treatment efficacy in colorectal cancer.

作者信息

Wang Yunshuai, Li Zhaohui, Li Wenxian, Liu Shuaifeng, Han Baowei

机构信息

Department of Gastrointestinal Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, P.R. China.

出版信息

Oncol Lett. 2018 Jul;16(1):195-198. doi: 10.3892/ol.2018.8670. Epub 2018 May 8.

Abstract

The aim of the present study was to examine the diagnosis of methylation of CDX2 gene promoter in colorectal cancer (CRC) and assessed its value in the prediction of treatment efficacy. Sixty patients who were diagnosed as CRCs for the first time, 60 patients with hyperplastic polyps (HPs) and adenomas, and 60 patients with inflammatory lesions or healthy patients (control group) were included in the present study. The methylation levels of CDX2 gene promoter were detected by methylation-specific polymerase chain reaction (MSP), and the expression levels of CDX2 mRNA were detected by fluorescence quantitative PCR. Treatment options, such as surgery, radiotherapy and chemotherapy, were chosen on the basis of TNM staging of CRC patients. The tumor-free survival, relapse rate and mortality were also recorded. The methylation rate was 71.67% (43/60) and significantly higher in the CRC group as compared to the HP/adenoma and control groups, P<0.05. Moreover, they showed further increase with higher degree of TNM staging. The expression levels of CDX2 mRNA was significantly lower in the CRC group in comparison to HP/adenoma and control groups, P<0.05, and showed a further decrease with a higher degree of TNM staging. The tumor-free survival was shorter, and the relapse rate and mortality were higher in patients with positive methylation in the CRC group, P<0.05. Multivariate logistic regression analysis demonstrated that TNM staging and positive methylation were independent risk factors of mortality. In conclusion, higher methylation degree of CDX2 gene promoter resulted in decreased expression of gene, and was closely associated with TNM staging and prognosis. TNM staging and positive methylation were independent risk factors of mortality for CRC patients.

摘要

本研究旨在探讨结直肠癌(CRC)中CDX2基因启动子甲基化的诊断情况,并评估其在预测治疗疗效中的价值。本研究纳入了60例首次诊断为CRC的患者、60例患有增生性息肉(HP)和腺瘤的患者以及60例患有炎性病变的患者或健康患者(对照组)。采用甲基化特异性聚合酶链反应(MSP)检测CDX2基因启动子的甲基化水平,采用荧光定量PCR检测CDX2 mRNA的表达水平。根据CRC患者的TNM分期选择手术、放疗和化疗等治疗方案。还记录了无瘤生存期、复发率和死亡率。CRC组的甲基化率为71.67%(43/60),与HP/腺瘤组和对照组相比显著更高,P<0.05。此外,随着TNM分期程度的升高,甲基化率进一步增加。与HP/腺瘤组和对照组相比,CRC组中CDX2 mRNA的表达水平显著更低,P<0.05,并且随着TNM分期程度的升高进一步降低。CRC组中甲基化呈阳性的患者无瘤生存期更短,复发率和死亡率更高,P<0.05。多因素逻辑回归分析表明,TNM分期和甲基化呈阳性是死亡率的独立危险因素。总之,CDX2基因启动子甲基化程度较高导致该基因表达降低,并且与TNM分期和预后密切相关。TNM分期和甲基化呈阳性是CRC患者死亡率的独立危险因素。

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引用本文的文献

本文引用的文献

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Clinical stage and risk of recurrence and mortality: interaction of DNA methylation factors in patients with colorectal cancer.
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Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients.
World J Gastroenterol. 2015 Feb 7;21(5):1457-67. doi: 10.3748/wjg.v21.i5.1457.
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