Birknerová Natália, Kovaříková Helena, Baranová Ivana, Přikrylová Albína, Laco Jan, Vošmiková Hana, Gajdošová Barbora, Hodek Miroslav, Vošmik Milan, Palička Vladimír, Chmelařová Marcela
Department of Clinical Biochemistry and Diagnostics, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic.
The Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic.
Epigenetics. 2022 Nov;17(11):1301-1310. doi: 10.1080/15592294.2021.2018812. Epub 2022 Jan 3.
Recently, 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 (P < 0.01) and (P < 0.05) genes. and hypermethylation was detected mostly in HPV-positive samples; all but one HPV-negative samples were unmethylated. Moreover, hypermethylation of gene 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.
最近，人们观察到人乳头瘤病毒（HPV）诱导的口咽鳞状细胞癌（OPSCC）发病率不断上升。此外，局部晚期阶段需要联合治疗方法，且预后较差。因此，找到早期诊断和预后生物标志物至关重要。DNA甲基化变化在致癌过程中起着关键作用，并且在许多类型的癌症中常被作为有前景的生物标志物进行研究。为了分析HPV阳性和HPV阴性样本（包括转移性OPSCC的原发性肿瘤和相应转移灶、非转移性OPSCC的原发性肿瘤以及对照样本）中选定肿瘤抑制基因的DNA甲基化水平，使用了甲基化特异性多重连接探针扩增技术（MLPA）和甲基化特异性高分辨率熔解分析。在[具体基因1]（P < 0.01）和[具体基因2]（P < 0.05）基因中观察到OPSCC与对照组之间甲基化存在显著差异。[具体基因1]和[具体基因2]的高甲基化大多在HPV阳性样本中检测到；除一个样本外，所有HPV阴性样本均未甲基化。此外，与对照样本相比，在转移灶中观察到[具体基因3]基因的高甲基化，并且这也与所有患者较短的总生存期相关（P < 0.05）。本文所述的选定基因启动子甲基化与临床病理数据之间的关联，未来可能通过改善疾病的筛查、早期检测和预后而使OPSCC患者受益。
