Methylation in the promoter regions of WT1, NKX6-1 and DBC1 genes in cervical cancer tissues of Uygur women in Xinjiang

Abstract

This study aimed to explore: 1) DNA methylation in the promoter regions of Wilms tumor gene 1 (WT1), NK6 transcription factor related locus 1 gene (NKX6-1) and Deleted in bladder cancer 1 (DBC1) gene in cervical cancer tissues of Uygur women in Xinjiang, and 2) the correlation of gene methylation with the infection of HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues, 30 cervical intraepithelial neoplasia lesions (CIN) and 48 cervical cancer tissues with polymerase chain reaction (PCR) method. Methylation in the promoter regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was measured by methylation-specific PCR (MSP) and cloning sequencing. The expression level of these three genes was measured by real-time PCR (qPCR) in 10 methylation-positive cervical cancer tissues and 10 methylation-negative normal cervical tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1 and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7 and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues. Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade squamous intraepithelial lesion (CIN2, CIN3) and in the cervical cancer tissues with infection of HPV16/18 (both P< 0.05). The expression of WT1, NKX6-1 and DBC1 was significantly lower in the methylation-positive cervical cancer tissues than in methylation-negative normal cervical tissues. Our findings indicated that methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be correlated with methylation in these genes. Gene inactivation caused by methylation might be related to the incidence and development of cervical cancer.

The clinical significance of HOXA9 promoter hypermethylation in head and neck squamous cell carcinoma

“…Head and neck squamous cell carcinoma is a complex disease that can affect multiple sites and is caused by intricate interactions among genetic susceptibility, epigenetic modification, and environmental factors . Emerging evidence indicates that epigenetic inactivation of tumor suppressor genes (TSGs) resulting from promoter methylation is involved in the onset and progress of various cancers, including esophageal squamous cell carcinoma, cervical cancer, lung cancer, and breast cancer . Aberrant methylation events are frequent, chemically stable, and relatively early molecular changes during carcinogenesis, which have potential as biomarkers for cancer screening and early diagnosis …”

SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis

“…Finally, 3491 patients with CC or CIN from 17 articles (Lai et al, 2008 , 2010 , 2014 ; Apostolidou et al, 2009 ; Xu et al, 2010 ; Chang et al, 2014 , 2015a , b ; Kan et al, 2014 ; Lin et al, 2014 ; Liu et al, 2016 ; Wang et al, 2016 ; Wu, 2016 ; Tian et al, 2017 ; Yuan, 2017 ; Rogeri et al, 2018 ; Robert et al, 2019 ) were included in this meta-analysis. Among these articles, 12 articles including 434 CC patients and 1,029 controls were used to analyze the correlation between SOX1 promoter methylation and clinicopathological features.…”

“…Among these articles, 12 articles including 434 CC patients and 1,029 controls were used to analyze the correlation between SOX1 promoter methylation and clinicopathological features. Among these 17 articles, 12 used exfoliated cells of cervical specimen to detect SOX1 methylation status, 3 (Xu et al, 2010 ; Pun et al, 2015 ; Wu, 2016 ) used cervical tissues, and 2 (Chang et al, 2014 ; Wang et al, 2016 ) involved both tissues and cervical exfoliated cells. For most of these 14 studies (14 of 17), the detection of SOX1 promoter methylation was performed by QMSP.…”

Role of Regulatory B Cells in the Progression of Cervical Cancer

“…The prevalence of cervical cancer in Xinjiang Uygur women (459-590/10 million) and mortality (15.78/10 million) were significantly higher than those of other ethnic groups living in the same environment [14]. Besides, the onset of cervical cancer in Xinjiang Uygur women is significantly earlier than that of other ethnic groups.…”