The promising role of PAX1 (aliases: HUP48, OFC2) gene methylation in cancer screening.

Chao Fang,Kai‐Ming Duan,Yu‐Ligh Liou,Wen Ouyang,Sai‐Ying Wang,Ming‐Hua Chen

doi:10.1002/mgg3.506

Chao Fang, Kai‐Ming Duan + Show 4 more

Open Access

https://doi.org/10.1002/mgg3.506

Copy DOI

Abstract

Background Paired‐box gene 1 (PAX1), a member of the PAX family, plays a role in pattern formation during embryogenesis, and might be essential for development of the vertebral column.Methods PAX1 is silenced by methylation in several cancers and is considered a tumor suppressor gene. Our previous studies reported PAX1 as hypermethylated in cervical cancer tissues, thereby suggesting it as a potential screening marker. Recently, an increasing number of studies have confirmed PAX1 methylation as a promising biomarker in cervical cancer based on its excellent discriminatory ability between high‐grade cervical lesions and normal tissues, resulting in a reduced necessity for referral for colposcopy and biopsy. Additionally, PAX1 is also hypermethylated in other tumors, including those associated with epithelial ovarian cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, and endometrial carcinoma, and shows relatively good sensitivity and specificity for the detection of these tumors.ResultsThis review summarizes reports of PAX1 methylation and its promising role in cancer screening, especially that associated with cervical cancer.ConclusionAccording to current evidence, combined testing for human papillomavirus and PAX1 methylation analysis represents an efficacious cervical cancer‐screening protocol.

Highlights

Paired‐box gene 1 (PAX1) (OMIM: 167,411) gene, a member of the PAX family located on chromosome 20p11.2, is essential to regulate fetal development. (Schnittger et al, 1992)
These data suggested the efficacy of PAX1 methylation as a biomarker for cervical cancer screening, and that it plays a guiding role in triage management of low‐grade squamous intraepithelial lesion (LSIL), high‐grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) patients, as well as displays higher accuracy than single human papillomavirus (HPV)‐DNA testing
Numerous studies have demonstrated that PAX1 methylation plays an important role in the progression of cancers and contributes significantly to the sensitivity and specificity of cancer screening, especially for cervical cancer

Summary

Introduction

PAX1 (OMIM: 167,411) gene, a member of the PAX family located on chromosome 20p11.2, is essential to regulate fetal development. (Schnittger et al, 1992). Multiple studies confirmed PAX1 methylation as the most highly correlated with CIN progression and cervical carcinogenesis (Chang et al, 2014; Chao et al, 2013; Chen et al, 2016; Huang et al, 2010; Kan et al, 2014; Lai et al, 2010, 2014; Luan et al, 2017; Tian et al, 2017; Xu et al, 2015). 15 individual studies showed that single PAX1 methylation allowed the accurate differential diagnosis of cervical cancer/ HSIL patients from normal individuals with a sensitivity of 0.80 and a specificity of 0.89 (Kong et al, 2015).

Results

Conclusion