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APC 启动子超甲基化作为乳腺癌患者的预后标志物。

APC Promoter Hypermethylation as a Prognostic Marker in Breast Cancer Patients.

机构信息

Research Division, National Cancer Institute, Bangkok 10400, Thailand.

Unit of Biochemistry, Department of Medical Sciences, Faculty of Science, Rangsit University, Patumthani, Thailand.

出版信息

Asian Pac J Cancer Prev. 2020 Dec 1;21(12):3627-3632. doi: 10.31557/APJCP.2020.21.12.3627.

Abstract

BACKGROUND

Adenomatous polyposis coli (APC) promoter hypermethylation implicated in breast cancer development through Wnt signaling pathway, hypermethylation may result in inactivation of APC expression. This study aimed to investigated whether hypermethylation of APC promoter, the aggressive behavior of breast cancer cells, and correlated them with clinicopathological parameters and survival.

METHODS

Sixty-one fresh tissues of breast tumor were evaluated for APC promoter hypermethylation with methylation-specific PCR techniques (MS-PCR) and  APC mRNA expression level analysis by quantitative real-time reverse transcription-PCR.

RESULTS

Our results show aberrant APC hypermethylation status was founded in 27 of 61 cases (44%), and significantly associated with chemotherapy treatment (OR= 6.9, 95%CI=1.5-31.01, P = 0.01), distant metastasis (OR = 5.52, 95%CI = 1.27-24.08, P = 0.04) as well as APC methylated status also associated with shorter overall survival than those without (8.4 and 11.0 years respectively, P = 0.02).

CONCLUSION

The findings indicated hypermethylation of APC promoter may be used as a useful prognostic biomarker in breast cancer patients.

摘要

背景

腺瘤性结肠息肉病(APC)启动子的异常甲基化通过 Wnt 信号通路参与乳腺癌的发生发展,其甲基化可能导致 APC 表达失活。本研究旨在探讨 APC 启动子的异常甲基化、乳腺癌细胞的侵袭性行为是否与临床病理参数和生存相关。

方法

采用甲基化特异性 PCR(MS-PCR)技术检测 61 例新鲜乳腺癌组织中 APC 启动子的异常甲基化状态,并通过实时定量逆转录-PCR 分析 APC mRNA 的表达水平。

结果

我们的结果显示,在 61 例病例中有 27 例(44%)存在 APC 异常甲基化,且与化疗治疗(OR=6.9,95%CI=1.5-31.01,P=0.01)、远处转移(OR=5.52,95%CI=1.27-24.08,P=0.04)显著相关,且 APC 甲基化状态与无 APC 甲基化状态的患者相比,总生存时间更短(分别为 8.4 年和 11.0 年,P=0.02)。

结论

这些发现表明 APC 启动子的异常甲基化可能可作为乳腺癌患者的一种有用的预后生物标志物。

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