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Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse
Article first published online: 19 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 18, pages 4266–4274, 15 September 2010
How to Cite
Lai, H.-C., Lin, Y.-W., Huang, R.-L., Chung, M.-T., Wang, H.-C., Liao, Y.-P., Su, P.-H., Liu, Y.-L. and Yu, M.-H. (2010), Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse. Cancer, 116: 4266–4274. doi: 10.1002/cncr.25252
- Issue published online: 3 SEP 2010
- Article first published online: 19 AUG 2010
- Manuscript Accepted: 4 JAN 2010
- Manuscript Revised: 14 DEC 2009
- Manuscript Received: 20 OCT 2009
- Tri-Service General Hospital. Grant Numbers: TSGH-C98-07-S01, S02, S03
- National Science Council, Republic of China. Grant Number: NSC98-2314-B-016-030-MY3
- Department of Health, Taiwan, ROC. Grant Number: DOH98-TD-I-111-TM003
- Advancement of Education, Sciences, and Medicine
- Teh-Tzer Study Group for Human Medical Research Foundation
- cervical intraepithelial neoplasm;
- cervical cancer;
- quantitative methylation-specific polymerase chain reaction
DNA methylation may be used a potential biomarker for detecting cervical cancer. The authors of this report used quantitative methylation analysis of 4 genes in a full spectrum of cervical lesions to test its potential clinical application.
This hospital-based, retrospective, case-control study was conducted in 185 patients and included patients who had a normal uterine cervix (n = 53), cervical intraepithelial neoplasm type 1 (CIN1) (n = 37), CIN2 (n = 22), CIN3 (n = 24), carcinoma in situ (CIS) (n = 22), squamous cell carcinoma (SCC, n = 20), and adenocarcinoma (AC) (n = 7). Methylation levels of the genes sex-determining region Y, box 1 (SOX1); paired box gene 1 (PAX1); LIM homeobox transcription factor 1α (LMX1A), and NK6 transcription factor-related locus 1 (NKX6-1) were determined by using real-time methylation-specific polymerase chain reaction (PCR) amplification. Cutoff values of the percentage of methylation reference (PMR) for different diagnoses were determined to test the sensitivity and specificity and to generate receiver operating characteristic (ROC) curves. Two-sided Mann-Whitney U tests were used to test differences in PMR between groups.
The PMRs of the 4 genes were significantly higher in CIN3 and worse (CIN3+) lesions than the PMRs in specimens of normal cervix and CIN1 or CIN2 (P < .001). ROC curve analysis demonstrated that the sensitivity, specificity, and accuracy for detecting CIN3+ lesions were 0.88, 0.82, and 0.95, respectively, for SOX1; 0.78, 0.91, and 0.89, respectively, for PAX1; 0.77, 0.88, and 0.90, respectively, for LMX1A; and 0.93, 0.97, and 0.97, respectively, for NKX6-1.
The current results indicated that quantitative PCR-based testing for DNA methylation of 4 genes holds great promise for cervical cancer screening and warrants further population-based studies using standardized DNA methylation testing. Cancer 2010. © 2010 American Cancer Society.