High Methylation Rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 Genes in Cervical Adenocarcinoma

Chang, Cheng-Chang MD*†‡; Huang, Rui-Lan PhD†§; Wang, Hui-Chen BS; Liao, Yu-Ping MS; Yu, Mu-Hsien MD, PhD*; Lai, Hung-Cheng MD, PhD*†‡§

International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0000000000000054
Basic Science
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 ZNF582—commonly methylated in squamous cell carcinomas—which might help for AC screening.

Author Information

*Department of Obstetrics and Gynecology, Tri-Service General Hospital; †Laboratory of Epigenetics and Cancer Stem Cells, and ‡Graduate Institute of Medical Sciences, National Defense Medical Center; and §Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China.

Address correspondence and reprint requests to Hung-Cheng Lai, MD, PhD, Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, 5F, No. 325, Sec 2, Cheng-Gong Rd, Neihu District, Taipei City 114, Taiwan, Republic of China. Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, No.291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561, Taiwan. E-mail: hclai@ndmctsgh.edu.tw.

This work was supported in part by the following grants: TSGH-C96-2-S01-4 from the Tri-Service General Hospital, NSC95-2622-B-016-001 and NSC95-2314-B-016-058-MY2 from the National Science Council, Republic of China, and the Teh-Tzer Study Group for Human Medical Research Foundation.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

The authors declare no conflicts of interest.

Received August 20, 2013

Received in revised form October 29, 2013

Accepted October 31, 2013

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.