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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Detection of HOXA9 gene methylation in tumor tissues and induced sputum samples from primary lung cancer patients

Sang-Hyun Hwang1, 3, a / Ki Uk Kim2, a / Ji-Eun Kim2 / Hyung-Hoi Kim1, 3 / 2, 5 / Chang Hun Lee4 / Sang-Yull Lee5 / TaeJeong Oh6 / Sungwhan An6

1Department of Laboratory Medicine, Pusan National University Hospital, School of Medicine Pusan National University, Busan, Republic of Korea

2Department of Internal Medicine, Pusan National University Hospital, School of Medicine Pusan National University, Busan, Republic of Korea

3Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea

4Department of Pathology, Pusan National University Hospital, School of Medicine Pusan National University, Busan, Republic of Korea

5Department of Biochemistry, School of Medicine Pusan National University, Busan, Republic of Korea

6Genomictree Inc., Daejeon, Republic of Korea

aSang-Hyun Hwang and Ki Uk Kim contributed equally as first co-authors.

Corresponding author: Min Ki Lee, MD, PhD, Department of Internal Medicine, Pusan National University Hospital, School of Medicine, Pusan National University, 1-10 Ami-dong Seo-gu, Busan 602-739, Republic of Korea Phone: +82-51-240-7216, Fax: +82-51-247-6560

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 49, Issue 4, Pages 699–704, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2011.108, April 2011

Publication History

Received:
2010-07-22
Accepted:
2010-11-11

Abstract

Background: Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening modality exists for lung cancer. We aimed to evaluate the prevalence of HOXA9 promoter methylation in tissue and induced sputum samples from Korean patients with lung cancer.

Methods: Using pyrosequencing, HOXA9 methylation was analyzed for 40 pairs of primary lung cancer and normal tissues and 185 induced sputum specimens, including 76 patients with lung cancer.

Results: The methylation of HOXA9 in lung cancer tissue was significantly higher compared with normal tissues (67.4%±17.6% vs. 23.6%±10.3%, respectively; p<0.001). With a cut-off of >45.6% of HOXA9 gene methylation in tissues, the sensitivity was 90.5% and the specificity was 97.5%. In induced sputum specimens, the HOXA9 gene in lung cancer patients was significantly more hypermethylated compared with patients with benign lung diseases and the healthy group (23.4%±15.9%, 14.9%±7.9%, and 9.7%±5.0%, respectively; p<0.001).

Conclusions: The HOXA9 gene was hypermethylated in 32 of 40 tumors (80%), especially in early stages of lung cancer. HOXA9 methylation could be a potential biomarker to aid early detection and prognosis.

Keywords: biomarker; DNA methylation; early detection; HOXA9 gene; lung cancer

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