Secreted frizzled-related protein promotors are hypermethylated in cutaneous squamous carcinoma compared with normal epidermis

Abstract

BackgroundThe Wnt signaling pathway is abnormally activated in many human cancers. Secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. SFRP promoter hypermethylation has often been identified in human cancers; however, the precise role of SFRPs in cutaneous squamous cell carcinoma (SCC) is unclear.MethodsThe methylation status of the SFRP family was analyzed in an age-and sex-matched case-control study, including 40 cutaneous SCC cases and 40 normal controls, using the MassARRAY EpiTYPER system.ResultsThe methylation rate of SFRP1, SFRP2, SFRP4, and SFRP5 promoters was significantly higher in cutaneous SCC tissues than in adjacent tissue and normal skin samples.DiscussionOur manuscript mainly discussed the average methylation rate of SFRPs (SFRP1, SFRP2, SFRP4, and SFRP5) promoters are significantly high in tumor tissue samples and the average CpG island methylation rate among different pathological levels of cutaneous SCC between these genes are different.ConclusionsOur findings suggest that promoter hypermethylation of SFRPs is associated with the development of carcinoma, and could be a useful tumor marker for cutaneous SCC and other types of cancers.

Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma

“…In fact, the KEGG analysis identifies important signalling pathways like MAPK, Notch, Wnt, TFGβ and hedgehog pathways, as potential pathways missregulated in the transition to a highrisk stage. It is important to remark that epigenetic alterations in other genes related to the Wntsignalling pathway had been previously reported in cSCC samples [30,31], as well as genetic mutation in Notch receptors [8,9,13]; our results supports a more broad extension of epigenetic alterations in the Wnt pathway and point to a combination of genetic and epigenetic alterations in the deregulation of the Notch pathway in cSCC.…”

“…The deregulation of the methylome is a hallmark of the development and progression of human cancers [24] and the altered DNA methylation patterns can be used as biomarkers for tumour detection, diagnosis and prognosis [23,25]. In the case of cSCC, previous studies targeting specific genes have reported promoter hypermethylation associated with the disease in genes such as cell cycle regulator CDKN2A [22], cadherin CDH1 [26,27] and CDH13 [28], transcription factor FOXE1 [29], modulators of Wnt signalling SFRPs [30] and FRZB [31], positive regulators of apoptosis ASC [32], G0S2 [33] and DAPK1 [34], and miRNA-204 [35], as well as hypomethylation of the DSS1 gene [36]. However, both DNA hypermethylation and hypomethylation associated with cancer is observed throughout the genome and these alterations, in particular the loss of methylation, may have functional consequences beyond regulation of proximal genes [24].…”

Genetic Polymorphisms of PGF and TNFAIP2 Genes Related to Cervical Cancer Risk Among Uygur Females from China

“…Table 1). These candidate SNPs were genotyped with Agena MassARRAY system (Agena, San Diego, CA, U.S.A.) as described previously (11,12), and conducted by two laboratory technicians doubleblinded. The primers for PCR ampli cation and single base extension were designed using the Assay Design 3.0 software (Supplementary Table 2).…”

WNT Signaling in Cutaneous Squamous Cell Carcinoma: A Future Treatment Strategy?

“…Furthermore, epigenetic profiling of metastatic cSCC compared to non-metastatic tumours, identified the FrzB gene, which encodes for the secreted WNT inhibitor, SFRP3, as having the most hypermethylated promoter in human cSCC, suggesting that loss of SFRP3 expression and subsequent WNT activation is a critical step in the development of metastatic tumours (Darr, et al 2015). Indeed, hypermethylation of a number of other SFRP genes (SFRP1, 2, 4 and 5) have also been identified in cSCC tumours compared to normal human skin (Liang, et al 2015). Further work is needed to fully understand the effects of the WNT signaling network in the metastatic progression of cSCC.…”