Methylation status, mRNA and protein expression of the SMAD4 gene in patients with non-melanocytic skin cancers

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dc.authoridbudak, metin/0000-0002-5968-2048
dc.authoridGURSEL URUN, Yildiz/0000-0002-6137-8395
dc.authorwosidBudak, metin/Z-3010-2019
dc.contributor.authorUrun, Yildiz Gursel
dc.contributor.authorBudak, Metin
dc.contributor.authorKeskin, Elif Usturali
dc.date.accessioned2024-06-12T10:54:12Z
dc.date.available2024-06-12T10:54:12Z
dc.date.issued2023
dc.departmentTrakya Üniversitesien_US
dc.description.abstractBackground SMAD4 is a potent tumor suppressor. SMAD4 loss increases genomic instability and plays a critical role in the DNA damage response that leads to skin cancer development. We aimed to investigate SMAD4 methylation effects on mRNA and protein expression of SMAD4 in cancer and healthy tissues from patients with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and basosquamous skin cancer (BSC). Methods and results The study included 17 BCC, 24 cSCC and nine BSC patients. DNA and RNA were isolated from cancerous and healthy tissues following punch biopsy. Methylation-specific polymerase chain reaction ( PCR) and real-time quantitative PCR methods were used to examine SMAD4 promoter methylation and SMAD4 mRNA levels, respectively. The percentage and intensity of staining of the SMAD4 protein were determined by immunohistochemistry. The percentage of SMAD4 methylation was increased in the patients with BCC (p = 0.007), cSCC (p = 0.004), and BSC (p = 0.018) compared to the healthy tissue. SMAD4 mRNA expression was decreased in the patients with BCC (p.0.001), cSCC (p.0.001), and BSC (p = 0.008). The staining characteristic of SMAD4 protein was negative in the cancer tissues of the patients with cSCC (p = 0.00). Lower SMAD4 mRNA levels were observed in the poorly differentiated cSCC patients ( p = 0.001). The staining characteristics of the SMAD4 protein were related to age and chronic sun exposure. Conclusions Hypermethylation of SMAD4 and reduced SMAD4 mRNA expression were found to play a role in the pathogenesis of BCC, cSCC, and BSC. A decrease in SMAD4 protein expression level was observed only in cSCC patients. This suggests that epigenetic alterations to the SMAD4 gene are associated with cSCC.en_US
dc.description.sponsorshipTrakya University Research Project Fund [2020/55]en_US
dc.description.sponsorshipThis study was supported by the Trakya University Research Project Fund (2020/55).en_US
dc.identifier.doi10.1007/s11033-023-08656-2
dc.identifier.endpage7304en_US
dc.identifier.issn0301-4851
dc.identifier.issn1573-4978
dc.identifier.issue9en_US
dc.identifier.pmid37428273en_US
dc.identifier.scopus2-s2.0-85164364404en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage7295en_US
dc.identifier.urihttps://doi.org/10.1007/s11033-023-08656-2
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18970
dc.identifier.volume50en_US
dc.identifier.wosWOS:001026555900001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofMolecular Biology Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectBasal Cell Carcinomaen_US
dc.subjectSquamous Cell Carcinomaen_US
dc.subjectSMAD4 Proteinen_US
dc.subjectDNA Methylationen_US
dc.subjectMrnaen_US
dc.subjectSquamous-Cell Carcinomaen_US
dc.titleMethylation status, mRNA and protein expression of the SMAD4 gene in patients with non-melanocytic skin cancersen_US
dc.typeArticleen_US

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