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DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer

Jian Zhu1, Yuyan Wang1, Jianchun Duan1, Hua Bai1, Zhijie Wang1, Lai Wei2, Jun Zhao1, Minglei Zhuo1, Shuhang Wang1, Lu Yang1, Tongtong An1, Meina Wu1 and Jie Wang1*

Author Affiliations

1 Department of Thoracic Medical Oncology Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, 100036, China

2 Laboratory of Immunology, National Eye Institute, National Institutes of Health, 31 Center Drive MSC 2510, Bethesda, MD, 20892-2510, USA

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Journal of Experimental & Clinical Cancer Research 2012, 31:80  doi:10.1186/1756-9966-31-80

Published: 25 September 2012

Abstract

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.

Keywords:
DNA methylation; EGFR-TKI; Wnt antagonists; Non-small cell lung cancer