High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma

Cheng Chang Chang, Rui Lan Huang, Hui Chen Wang, Yu Ping Liao, Mu Hsien Yu, Hung Cheng Lai

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objective: This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix. Methods: We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing. Results: The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95% confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95% CI, 7.0-40.6), 16.9 (95% CI, 7.6-43.0), 32.1 (95% CI, 12.1-124.3), and 25.4 (95% CI, 10.4-78.3), respectively (all P <0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95% CI, 2.6-15.4), 12.1(95% CI, 3.8-46.4), 6.2 (95% CI, 2.6-15.8), and 20.6 (95% CI, 6.9-77.5), respectively (all P <0.001). Conclusions: Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582Vcommonly methylated in squamous cell carcinomas - which might help for AC screening.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalInternational Journal of Gynecological Cancer
Volume24
Issue number2
DOIs
Publication statusPublished - Jan 2014

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Methylation
Adenocarcinoma
Confidence Intervals
Genes
Cervix Uteri
Squamous Cell Carcinoma
Odds Ratio
DNA Methylation
Polymerase Chain Reaction

Keywords

  • Adenocarcinoma of the cervix
  • Bisulfite pyrosequencing
  • DNA methylation
  • Real-time quantitative methylation-specific PCR

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma. / Chang, Cheng Chang; Huang, Rui Lan; Wang, Hui Chen; Liao, Yu Ping; Yu, Mu Hsien; Lai, Hung Cheng.

In: International Journal of Gynecological Cancer, Vol. 24, No. 2, 01.2014, p. 201-209.

Research output: Contribution to journalArticle

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abstract = "Objective: This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix. Methods: We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing. Results: The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95{\%} confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95{\%} CI, 7.0-40.6), 16.9 (95{\%} CI, 7.6-43.0), 32.1 (95{\%} CI, 12.1-124.3), and 25.4 (95{\%} CI, 10.4-78.3), respectively (all P <0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95{\%} CI, 2.6-15.4), 12.1(95{\%} CI, 3.8-46.4), 6.2 (95{\%} CI, 2.6-15.8), and 20.6 (95{\%} CI, 6.9-77.5), respectively (all P <0.001). Conclusions: Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582Vcommonly methylated in squamous cell carcinomas - which might help for AC screening.",
keywords = "Adenocarcinoma of the cervix, Bisulfite pyrosequencing, DNA methylation, Real-time quantitative methylation-specific PCR",
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T1 - High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma

AU - Chang, Cheng Chang

AU - Huang, Rui Lan

AU - Wang, Hui Chen

AU - Liao, Yu Ping

AU - Yu, Mu Hsien

AU - Lai, Hung Cheng

PY - 2014/1

Y1 - 2014/1

N2 - Objective: This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix. Methods: We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing. Results: The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95% confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95% CI, 7.0-40.6), 16.9 (95% CI, 7.6-43.0), 32.1 (95% CI, 12.1-124.3), and 25.4 (95% CI, 10.4-78.3), respectively (all P <0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95% CI, 2.6-15.4), 12.1(95% CI, 3.8-46.4), 6.2 (95% CI, 2.6-15.8), and 20.6 (95% CI, 6.9-77.5), respectively (all P <0.001). Conclusions: Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582Vcommonly methylated in squamous cell carcinomas - which might help for AC screening.

AB - Objective: This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix. Methods: We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing. Results: The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95% confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95% CI, 7.0-40.6), 16.9 (95% CI, 7.6-43.0), 32.1 (95% CI, 12.1-124.3), and 25.4 (95% CI, 10.4-78.3), respectively (all P <0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95% CI, 2.6-15.4), 12.1(95% CI, 3.8-46.4), 6.2 (95% CI, 2.6-15.8), and 20.6 (95% CI, 6.9-77.5), respectively (all P <0.001). Conclusions: Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582Vcommonly methylated in squamous cell carcinomas - which might help for AC screening.

KW - Adenocarcinoma of the cervix

KW - Bisulfite pyrosequencing

KW - DNA methylation

KW - Real-time quantitative methylation-specific PCR

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