Quantitative Analysis of Methylation Status of the PAX1 Gene for Detection of Cervical Cancer

Huang, Tien Hung; Lai, Hung Chen; Liu, Hwan Wun; Lin, Cuei Jyuan; Wang, Kai-Hung; Ding, Dah‐Ching; Chu, Tang-Yuan

doi:10.1111/igc.0b013e3181c7fe6e

Cited by 42 publications

(37 citation statements)

References 27 publications

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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: 90%

“…Inactivation of PAX1 has been observed in patients with CC and is considered to be associated with the methylation of the promoter region (47,48). In a hospital-based study on CC detection, Huang et al (49) observed that the quantitative measurement of PAX1 hypermethylation in cervical samples was highly sensitive and more specific compared with the Hybrid Capture 2 HPV test (0 vs. 5.9% in normal tissue). In the past, the study of PAX1 gene methylation in the cervix was found to be used for the differential diagnosis of invasive carcinoma (50).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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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“…Consistent with these findings several studies showed that all (100%) cervical scrapings of women with underlying cervical cancer were positive for DNA methylation using PAX1 (n=14), TIMP3 (n=11), or a tri-marker panel consisting of CADM1, MAL and hsamiR124-2 genes (n=79) (L., de Strooper and M., van Zummeren, personal communication) 114,115 .…”

Section: Hsa-mir-124-2 Panel Recently Passed the Later Phases Of Biommentioning

confidence: 64%

Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions

et al. 2014

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PrefaceInfection of cervical epithelium with high-risk human papillomavirus (hrHPV) might result in productive or transforming cervical intraepithelial neoplasia (CIN) lesions, the morphology of which can overlap. In transforming CIN lesions aberrations in host cell genes accumulate over time, which is necessary for ultimate progression to cancer. On the basis of (epi)genetic changes, early and advanced transforming CIN lesions can be distinguished. This paves the way for new molecular tools for cervical screening, diagnosis and management of cervical cancer precursor lesions.

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“…This has led to the idea that methylation analysis can provide an attractive early-detection biomarker, amongst others, to be used as triage method for hrHPV-positive women in cervical screening (3,9). Indeed, promising results have been obtained (10)(11)(12)(13)(14)(15) with sensitivities for CIN2þ [i.e., cervical intraepithelial neoplasia (CIN) grade 2 (CIN2), CIN3, and cervical cancer] and CIN3þ (i.e., CIN3 and cervical cancer) similar to those of cytology analysis on cervical scrapes (11,12), the latter currently being the most widely suggested triage tool. Of interest, recent work has revealed that methylation levels of several genes are particularly high in cervical scrapes of women with cervical cancer and advanced high-grade CIN lesions, the latter characterized by a longer duration (!5 years) of a preceding hrHPV infection (PHI; refs.…”

Section: Introductionmentioning

confidence: 99%

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

108

154

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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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Quantitative Analysis of Methylation Status of the PAX1 Gene for Detection of Cervical Cancer

Abstract: In this hospital-based study, quantitative measurement of PAX1 hypermethylation in cervical scrapings is highly sensitive and is more specific than HC2 in detection of cervical cancer.

Cited by 42 publications

References 27 publications

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

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

Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions

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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