Abstract
Purpose
Novel molecular predictive biomarkers for chemotherapy have been screened and validated in non-small cell lung cancer (NSCLC). However, there was no report on the correlation of genome-wide DNA methylation with survival benefit from chemotherapy in NSCLC.
Methods
A sandwich enzyme-linked immunosorbent assay (ELISA) method was first established, optimized and validated. A total of 191 NSCLC samples were analyzed using the sandwich ELISA for the association between the relative genome-wide DNA methylation level and the survival outcomes from chemotherapy.
Results
The analytical performance of the sandwich ELISA method was satisfying and suitable for analysis. Using the sandwich ELISA method, we found that the genome-wide DNA methylation level in NSCLC cancer tissues was significantly lower than that in adjacent normal tissues, which further validated the assay. We found that there was no significant correlation between genome-wide DNA methylation level and patients’ histology, stage and progression free survivals. However, in patients with high methylation level, those without chemotherapy had significantly better overall survival than those receiving chemotherapy. In patients receiving chemotherapy, those with low genome-wide DNA methylation level had significantly better overall survival than those with relatively high DNA methylation level.
Conclusions
Genome-wide DNA hypomethylation as a sign of genomic instability may predict overall survival benefit from chemotherapy in NSCLC.
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Acknowledgments
This work was supported by NIH/NCI R01CA125030 and the Eileen D. Ludwig Endowed for Thoracic Oncology Research (to B He); The Bonnie J. Addario Lung Cancer Foundation, the Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Harley & Oberman Foundation, the Ziegelmam Family Foundation and the Barbara Isackson Lung Cancer Research Fund (to DM Jablons); The Innovative Health Science and Technology Talent Project in Henan Province (to Y. Guo); The fund from Science and Technology of Xiaoshan District No. 2012121 (to H.M. Zhou); The fund from the Science and Technology Bureau of Jiaxing No. 2012AY1040 (to H.M. Zhou); and The China Natural Science Foundation No. 31170732 and No. 31270854 (to H.M. Zhou).
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We declare that we have no conflict of interest.
Ethical standard
Investigation has been conducted in accordance with the ethical standards and according to the Declaration of Helsinki, as well as national and international guidelines, and has been approved by the Committee on Human Research at the University of California, San Francisco.
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Min-Li Mo and Jie Ma have contributed equally to this work.
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Mo, ML., Ma, J., Chen, Z. et al. Measurement of genome-wide DNA methylation predicts survival benefits from chemotherapy in non-small cell lung cancer. J Cancer Res Clin Oncol 141, 901–908 (2015). https://doi.org/10.1007/s00432-014-1860-7
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DOI: https://doi.org/10.1007/s00432-014-1860-7