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Hypermethylation of collagen α2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer

Article type: Research Article

Authors: Misawa, Kiyoshia; * | Kanazawa, Takeharub | Misawa, Yukia | Imai, Atsushia | Endo, Shioria | Hakamada, Katsuraa | Mineta, Hiroyukia

Affiliations: [a] Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan | [b] Department of Otolaryngology/Head and Neck Surgery, Jichi Medical University, Tochigi, Japan

Correspondence: [*] Corresponding author: Kiyoshi Misawa, Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Shizuoka 431-3192, Japan. Tel.: +81 53 435 2252; Fax: +81 53 435 2253; E-mail: kiyoshim@hama-med.ac.jp.

Keywords: COL1A2, DNA methylation, CpG island, head and neck cancer, 5-azacytidine

DOI: 10.3233/CBM-2012-0242

Journal: Cancer Biomarkers, vol. 10, no. 3-4, pp. 135-144, 2012

Published: 25 May 2012
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Abstract

Objectives:

Collagen production plays a role in the development of tumors from cancer cells. The aim of the present study is to examine the involvement of epigenetic alteration of Collagen α2 (I) (COL1A2) gene expression in cases of head and neck squamous cell carcinoma (HNSCC).

Methods:

COL1A2 expression was examined in a panel of cell lines using RT-PCR. The methylation status of the COL1A2 promoter was studied using bisulfate sequencing and methylation-specific PCR (MSP).

Results:

COL1A2 expression was absent in 6 of 11 (54.5%) UM-SCC cell lines, whereas three nonmalignant cell lines had stable expressions. MSP analysis showed that 46/98 (46.9%) contained methylated alleles. COL1A2 methylation was significantly correlated with tumor size (P=0.041), lymph node status (P= 0.008), tumor stage (P=0.011), H-cadherin methylation (P=0.039) and disease-free survival (P=0.005). On multivariate Cox proportional hazard regression, which included age, sex, smoking status, and alcohol exposure, both tumor stage and COL1A2 methylation remained independent prognostic factors.

Conclusions:

This study suggests that CpG hypermethylation is a likely mechanism of COL1A2 gene inactivation, supporting the hypothesis that the COL1A2 gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker.

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