Aberrant methylation of secreted protein, acidic and rich in cysteine in human laryngeal and hypopharyngeal carcinoma

He,Qian; Wei,Jiazhang; Zhang,Jinyan; Jiang,Heng; Wang,Shumin; Zhou,Xiaoying; Zhang,Zhe; Huang,Guangwu; Watanabe,Hiroshi; Su,Jiping

doi:10.3892/ol.2011.297

Aberrant methylation of secreted protein, acidic and rich in cysteine in human laryngeal and hypopharyngeal carcinoma

Authors:
- Qian He
- Jiazhang Wei
- Jinyan Zhang
- Heng Jiang
- Shumin Wang
- Xiaoying Zhou
- Zhe Zhang
- Guangwu Huang
- Hiroshi Watanabe
- Jiping Su
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P.R. China, Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu 431‑3192, Japan, Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431‑3192, Japan
Published online on: May 5, 2011 https://doi.org/10.3892/ol.2011.297
Pages: 725-729

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Abstract

Secreted protein, acidic and rich in cysteine (SPARC) has been found to be involved in various stages of tumor progression such as migration, invasion, extracellular matrix deposition and angiogenesis. To obtain an insight into the role of SPARC in the progression of laryngeal and hypopharyngeal carcinoma, we investigated SPARC transcription levels and promoter methylation in carcinoma cell lines and primary tumors. Reverse transcription-PCR showed that SPARC was silenced in laryngeal and hypopharyngeal carcinoma cell lines, in which aberrant promoter methylation was detected. Hypermethylation of SPARC was detected in 56.1% (23/41) of laryngeal carcinoma and 70.0% (7/10) of hypopharyngeal carcinoma biopsies, but only in 11.1% (1/9) of normal epithelial specimens by a methylation-specific PCR assay. Bisulphite genomic sequencing indicated that CpG sites in the SPARC promoter were heavily methylated in cell lines and primary tumors. Moreover, pharmacological demethylation treatment rescued SPARC expression with 5-aza-2'-deoxycytidine (5-aza-dC) in the laryngeal carcinoma cell lines. SPARC promoter hypermethylation was significantly correlated with lymph node metastasis (p<0.01). Our findings suggest that hypermethylation of SPARC is a frequent and tumor-specific event in laryngeal and hypopharyngeal carcinomas and may serve as a biomolecular marker for diagnosis and prognosis.

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