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学科主题: 临床医学
题名:
DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer
作者: Zhu, Jian1; Wang, Yuyan1; Duan, Jianchun1; Bai, Hua1; Wang, Zhijie1; Wei, Lai2; Zhao, Jun1; Zhuo, Minglei1; Wang, Shuhang1; Yang, Lu1; An, Tongtong1; Wu, Meina1; Wang, Jie1
关键词: DNA methylation ; EGFR-TKI ; Wnt antagonists ; Non-small cell lung cancer
刊名: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
发表日期: 2012-09-25
DOI: 10.1186/1756-9966-31-80
卷: 31
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: GROWTH-FACTOR RECEPTOR ; ACUTE MYELOID-LEUKEMIA ; PROMOTER HYPERMETHYLATION ; SIGNALING PATHWAY ; EPIGENETIC INACTIVATION ; GEFITINIB ; MUTATIONS ; GENE ; CHEMOTHERAPY ; EXPRESSION
英文摘要:

Background: It is well known that genetic alternation of epidermal growth factor receptor (EGFR) plays critical roles in tumorgenesis of lung cancer and can predict outcome of non-small-cell lung cancer treatment, especially the EGFR tyrosine-kinase inhibitors (EGFR-TKIs) therapy. However, it is unclear whether epigenetic changes such as DNA methylation involve in the response to the EGFR-TKI therapy.

Methods: Tumor samples from 155 patients with stages IIIB to IV NSCLC who received EGFR-TKI therapy were analyzed for DNA methylation status of Wnt antagonist genes, including SFRP1, SFRP2, SFRP5, DKK3, WIF1, and APC, using methylation specific PCR (MSP) method. EGFR mutations detections were performed in the same tissues samples using Denaturing High Performance Liquid Chromatography (DHPLC).

Results: We found that Wnt antagonists tend to methylate simultaneously. Methylation of sFRP1 and sFRP5 are reversely correlated with EGFR mutation (P = 0.005, P = 0.011). However, no correlations of methylations of other Wnt antagonist genes with EGFR mutation were found. The patients with methylated SFRP5 have a significant shorter progression free survival than those with unmethylated SFRP5 in response to EGFR-TKI treatment (P = 0.002), which is independent of EGFR genotype.

Conclusions: Patients with unmethylated SFRP5 are more likely to benefit from EGFR-TKI therapy.

语种: 英语
所属项目编号: 81025012 ; 81172235 ; 2011-2-22
项目资助者: National Natural Sciences Foundation Distinguished Young Scholars ; National Natural Sciences Foundation General Program ; Beijing Health Systems Academic Leader
WOS记录号: WOS:000312598700001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63113
Appears in Collections:北京大学临床肿瘤学院_胸部肿瘤内科_期刊论文

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作者单位: 1.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Dept Thorac Med Oncol, Beijing 100036, Peoples R China
2.NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA

Recommended Citation:
Zhu, Jian,Wang, Yuyan,Duan, Jianchun,et al. DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2012,31.
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