DNA hypermethylation of CADM1, PAX5, WT1, RARβ, and PAX6genes in oropharyngeal cancer associated with human papillomavirus

Autor: Birknerová, Natália, Kovaříková, Helena, Baranová, Ivana, Přikrylová, Albína, Laco, Jan, Vošmiková, Hana, Gajdošová, Barbora, Hodek, Miroslav, Vošmik, Milan, Palička, Vladimír, Chmelařová, Marcela
Zdroj: Epigenetics; November 2022, Vol. 17 Issue: 11 p1301-1310, 10p
Abstrakt: ABSTRACTRecently, an increasing incidence of HPV-induced oropharyngeal squamous cell carcinoma (OPSCC) has been observed. Moreover, locoregionally advanced stages require a combined modal approach, and the prognosis is poor. Therefore, it is essential to find early diagnostic and prognostic biomarkers. DNA methylation changes play a crucial role in the process of carcinogenesis and are often investigated as promising biomarkers in many types of cancer. For analysis of DNA methylation levels of selected tumour suppressor genes in HPV-positive and HPV-negative samples (including primary tumours and corresponding metastases of metastasizing OPSCCs, primary tumours of non-metastasizing OPSCCs, and control samples), methylation-specific MLPA and methylation-specific high-resolution melting analyses were used. A significant difference in methylation between OPSCCs and the control group was observed in WT1, PAX6(P < 0.01) and CADM1, RARβ(P < 0.05) genes. CADM1and WT1hypermethylation was detected mostly in HPV-positive samples; all but one HPV-negative samples were unmethylated. Moreover, hypermethylation of PAX5gene was observed in metastases compared with control samples and was also associated with shorter overall survival of all patients (P < 0.05). Associations described herein between promoter methylation of selected genes and clinicopathological data could benefit OPSCC patients in the future by improvement in screening, early detection, and prognosis of the disease.
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