Methylation Biomarkers with Discriminating Ability are Potential Therapeutic Targets in Lung Adenocarcinoma

Abstract

Aims: Given the reversibility of methylation, biomarkers with discriminating ability are of great interest for targeted therapeutic sites. Materials & methods: Methylation array data of 461 lung adenocarcinoma (LUAD) patients comprising of 458 tumor and 32 LUAD paracancerous samples were compared using partial least squares discrimination analysis and receiver operating characteristics analysis. Results: A six-DNA methylation signature (corresponding to five genes) was found to significantly discriminate normal and LUAD samples. Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of methylation sites in the Wnt pathway in LUAD compared with controls. Conclusion: This six-DNA methylation signature demonstrated potential as a novel biomarker for diagnosis and therapeutic targets. Further, inhibition of Wnt signaling pathway may be an important step in LUAD progression.

Keywords::

• biomarker
• DNA methylation
• lung adenocarcinoma
• Notch signaling pathway
• therapeutic target
• tumor suppressor genes
• Wnt signaling pathway

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0142

Author Contributions

WW Zhao and K Li designed the study. ZW Rong and WJ Wang carried out the data analysis. YX Lu, K Yang and S Li interpreted the entire results and drafted the manuscript. K Deng, CY Yang and L Cao helped carry out the data analysis. All authors read and approved the final manuscript.

Acknowledgments

The results shown in this manuscript are based upon the data generated by The Cancer Genome Atlas Research Network: http://cancergenome.nih.gov/ and Gene Expression Omnibus data portal: www.ncbi.nlm.nih.gov/geo/

Financial & competing interests disclosure

This work was funded by National Natural Science Foundation of China under Grant number 81773551. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript

Additional information

Funding

This work was funded by National Natural Science Foundation of China under Grant number 81773551. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript