SFRP1 is a possible candidate for epigenetic therapy in non-small cell lung cancer

Abstract

Background: 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. 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.

Methods: This 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.

Results: The 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.

Conclusions: The meta-analysis of reprogrammed NSCLC cell lines identified SFRP1 as a promising target of epigenetic therapy for NSCLC.

Fig. 1

Hierarchical clustering of PCs. Vertical axes represent distance that is negative signed absolute correlation coefficients between PCs. PCs with “M” indicate promoter methylation and those without “M” were computed from gene expression

Fig. 2

Protein complex. a WNT1 (cyan) + SFRP1 (light green) by Fiberdock + ZDOCK, b WNT8 (cyan) + CRD of FZ8 (light green) by Fiberdock + ZDOCK, c WNT1(cyan) + SFRP1(light green) by GROMACS (time = 2 ns), d WNT8 (cyan) + CRD of Fz8 (light green) in PDB (PDB ID: 4F0A)

Fig. 3

RMSD for GROMACS MD for those from 0 ns to 1 ns and those from 1 ns to 2 ns