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Kan, Yuen-Yee; Liou, Yu-Ligh; Wang, Huei-Jen; Chen, Chiao‐Ying; Sung, Li-Chi; Chang, Chih-Hung; Liao, Cheng-I

doi:10.1097/igc.0000000000000155

Cited by 56 publications

(36 citation statements)

References 26 publications

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“…A published research suggested that the methylation test of PAX1 gene harbored higher diagnostic accuracy against HPV DNA testing in detecting cervical cancer (20). Similarly, other studies also documented that quantitative measurement of PAX1 hypermethylation in cervical scrapings is highly accurate than both SOX1 hypermethylation and HPV DNA assay, which the sensitivity was 0.86, and specificity was 0.85 under the ROC curve (12,17). Our results agree well with these data.…”

Section: Discussionsupporting

confidence: 82%

“…Among these altered and methylated genes, the paired boxed gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) were both highlighted (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Numerous studies have documented the promise of PAX1 or SOX1 DNA methylation in distinguishing patients with reactive atypia or CIN3+ (cervical intraepithelial neoplasia type III or worse) lesions from normal uterine cervixes (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). In order to make a comparison of the accuracy of DNA methylation and HPV DNA testing, we performed a comprehensive meta-analysis and evaluated the diagnostic performance of PAX1 and SOX1 methylation for cervical cancer screening.…”

Section: Introductionmentioning

confidence: 99%

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PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians

et al. 2016

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Background: Epigenetic alterations of gene or DNA methylation have been highlighted as promising biomarkers for early cervical cancer screening. Herein, we evaluated the diagnostic performance of paired boxed gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) methylation for cervical cancer detection.Methods: Eligible studies were retrieved by searching the electronic databases. Study quality was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 12.0 software. Conclusions: PAX1 or SOX1 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening, and parallel testing of PAX1 methylation and HPV DNA in cervical swabs confers an improved diagnostic accuracy than single HPV DNA testing.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians

et al. 2016

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“…These data revealed that the detection of PAX1 methylation has clinical diagnostic value in differentiating invasive CC, but may not be sufficient alone in screening for HSIL. A number of studies have indicated the potential value of PAX1 for the screening and detection of CC (49,51,52), in line with the findings of the present study, but the association between PAX1 and tumors requires further investigation. The present study used methylation-specific PCR to demonstrate that the PAX1 gene is abnormally methylated in cervical cancer specimens, with methylation rates as high as 87.5%, which is significantly different to those in normal cervical tissues and cervical precancerous lesions (49).…”

Section: Discussionsupporting

confidence: 81%

Quantitative DNA methylation analysis of paired box gene 1 and LIM homeobox transcription factor 1 α genes in cervical cancer

et al. 2018

Oncol Lett

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Abstract. DNA methylation is associated with tumorigenesis and may act as a potential biomarker for detecting cervical cancer. The aim of the present study was to explore the methylation status of the paired box gene 1 (PAX1) and the LIM homeobox transcription factor 1 α (LMX1A) gene in a spectrum of cervical lesions in an Eastern Chinese population. This single-center study involved 121 patients who were divided into normal cervix (NC; n=28), low-grade squamous intraepithelial lesion (LSIL; n=32), high-grade squamous intraepithelial lesion (HSIL; n=34) and cervical squamous cell carcinoma (CSCC; n=27) groups, according to biopsy results. Following extraction and modification of the DNA, quantitative assessment of the PAX1 and LMX1A genes in exfoliated cells was performed using pyrosequencing analysis. Receiver operating characteristic (ROC) curves were generated to calculate the sensitivity and specificity of each parameter and cut-off values of the percentage of methylation reference (PMR) for differentiation diagnosis. Analysis of variance was used to identify differences among groups. The PMR of the two genes was significantly higher in the HSIL and CSCC groups compared with that in the NC and LSIL groups (P<0.001). ROC curve analysis demonstrated that the sensitivity, specificity and accuracy for detection of CSCC were 0.790, 0.837 and 0.809, respectively, using PAX1; and 0.633, 0.357 and 0.893, respectively, using LMX1A. These results indicated that quantitative PAX1 methylation demonstrates potential for cervical cancer screening, while further investigation is required to determine the potential of LMX1A methylation.

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“…Here, we found that the FAM19A4 marker alone had a similar performance in terms of CIN2þ, CIN3þ, and cervical carcinoma detection as a panel of previously studied methylation markers (11). Recently, other single methylation markers, i.e., PAX1 and ZNF582, have been reported as a promising methylation markers for cervical screening and women with LSIL, respectively (30,31). Yet, these markers have not been validated in population-based screening studies and require further investigation.…”

Section: Discussionmentioning

confidence: 57%

Methylation Analysis of the FAM19A4 Gene in Cervical Scrapes Is Highly Efficient in Detecting Cervical Carcinomas and Advanced CIN2/3 Lesions

Strooper

Meijer

Berkhof

et al. 2014

Cancer Prevention Research

103

150

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Primary testing for human papillomavirus (HPV) in cervical screening requires triage to differentiate women with transient infection from those with persistent infection who require more intensive management given their risk for cervical (pre)cancer. In this study, the clinical performance of a novel methylation marker FAM19A4 for the triage of high-risk (hr)HPV-positive women was evaluated. Using a trainingvalidation set approach, we analyzed a FAM19A4 quantitative methylation-specific PCR (qMSP). The training set comprised hrHPV-positive cervical scrapes of 43 women with cervical intraepithelial neoplasia grade 3 or worse (CIN3þ) and 135 women with CIN1. The validation set comprised hrHPV-positive cervical scrapes of 52 women with CIN2þ, including 33 CIN3þ, 19 CIN2, and 166 women with CIN1. The methylation threshold of FAM19A4 qMSP that gave rise to CIN3þ specificity of 70% in the training set was applied in the validation set. This resulted in CIN3þ sensitivity of 75.8% [95% confidence interval (CI), 61.1-90.4] at 67.0% (95% CI, 60.3-73.8) specificity. Next, the validated qMSP was applied to an independent series of hrHPV-positive cervical scrapes of 22 women with cervical cancer, 29 with advanced CIN2/3 [i.e., women with a known preceding hrHPV infection (PHI) lasting !5 years as proxy of longer duration of lesion existence], and 19 with early CIN2/3 (i.e., PHI <5 years). All carcinomas (22/22) and advanced CIN2/3 lesions (29/29) were FAM19A4 methylation-positive, compared with 42.1% (8/19; 95% CI, 19.9-64.3) of early CIN2/3 lesions. In conclusion, FAM19A4 is an attractive triage marker for hrHPVpositive women, with a high reassurance for the detection of cervical carcinoma and advanced CIN2/3 lesions. Cancer Prev Res; 7(12); 1251-7. Ó2014 AACR.

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Atl

Cited by 56 publications

References 26 publications

PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians

PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians

Quantitative DNA methylation analysis of paired box gene 1 and LIM homeobox transcription factor 1 α genes in cervical cancer

Methylation Analysis of the FAM19A4 Gene in Cervical Scrapes Is Highly Efficient in Detecting Cervical Carcinomas and Advanced CIN2/3 Lesions

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