Abstract
BackgroundNon-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments. Recent studies have indicated that epigenetic therapy, which targets epigenetic effects, might be a new therapeutic methodology for NSCLC. However, it is not clear which objects (e.g., genes) this treatment specifically targets. Secreted frizzled-related proteins (SFRPs) are promising candidates for epigenetic therapy in many cancers, but there have been no reports of SFRPs targeted by epigenetic therapy for NSCLC.MethodsThis study performed a meta-analysis of reprogrammed NSCLC cell lines instead of the direct examination of epigenetic therapy treatment to identify epigenetic therapy targets. In addition, mRNA expression/promoter methylation profiles were processed by recently proposed principal component analysis based unsupervised feature extraction and categorical regression analysis based feature extraction.ResultsThe Wnt/β-catenin signalling pathway was extensively enriched among 32 genes identified by feature extraction. Among the genes identified, SFRP1 was specifically indicated to target β-catenin, and thus might be targeted by epigenetic therapy in NSCLC cell lines. A histone deacetylase inhibitor might reactivate SFRP1 based upon the re-analysis of a public domain data set. Numerical computation validated the binding of SFRP1 to WNT1 to suppress Wnt signalling pathway activation in NSCLC.ConclusionsThe meta-analysis of reprogrammed NSCLC cell lines identified SFRP1 as a promising target of epigenetic therapy for NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0196-3) contains supplementary material, which is available to authorized users.
Highlights
Non-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments
Identification of biologically significant genes To identify genes targeted by epigenetic therapy in NSCLC, we analysed gene expression and promoter methylation in reprogrammed NSCLC cell lines [8]
The primary aim of this analysis was to identify genes associated with aberrant gene expression and promoter methylation during reprogramming because associated genes are most likely targeted by epigenetic therapy
Summary
Non-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments. Recent studies have indicated that epigenetic therapy, which targets epigenetic effects, might be a new therapeutic methodology for NSCLC. It is not clear which objects (e.g., genes) this treatment targets. Non-small cell lung cancer (NSCLC) is still lethal despite many proposed therapeutic strategies. There has been extensive research regarding the clinical usefulness of epigenetic therapy for NSCLC; studies investigating the target genes of these treatments are limited, some promising candidates have been proposed [4]. A detailed and extensive comparative study might indirectly identify the effect of epigenetic therapy in NSCLC cell lines.
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