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Expression of 11 HOX Genes Is Deregulated in Esophageal Squamous Cell Carcinoma

Departments of ¹ Thoracic Surgery, ² Genetics, ³ Pathology, and ⁴ General Surgery, Peking University School of Oncology, Beijing Cancer Hospital, Beijing, China; and ⁵ Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang City, China

Requests for reprints: Ke-Neng Chen, Department of Thoracic Surgery, Peking University School of Oncology, Beijing Cancer Hospital, Beijing, China, 100036. Phone: 86-10-88121122; Fax: 86-10-88122437; E-mail: chenkeneng{at}yahoo.com.cn.

Purpose: HOX genes are vital for all aspects of mammalian growth and differentiation, and recent data have shown that their deregulated expression is related to carcinogenesis. To date, there has been no systemic study on expression of HOX genes in esophageal carcinoma. We investigated the expression pattern of 39 known HOX genes in cancerous and noncancerous tissue from 36 patients with esophageal squamous cell carcinoma to determine whether their expression is altered in esophageal cancer.

Experimental Design: Thirty-six patients with resectable esophageal squamous cell carcinoma (ESCC) were enrolled in this study. Specific primers were designed for each of 39 HOX genes, and reverse transcription-PCR was done in cancerous and noncancerous samples of these 36 patients. Furthermore, the expression of HOXA9 protein was subjected to Western blot analysis in all 36 paired tissue samples.

Results: Eight of 39 HOX genes were expressed in cancerous but not in noncancerous tissue. Five of 39 HOX genes were expressed both in cancerous and noncancerous tissue. Of the latter, expression of HOXA7, HOXA9, and HOXC6 was significantly higher in cancerous tissue (P < 0.05). The remaining 26 HOX genes were not detected in either types of tissue. HOXA9 protein was expressed in both kinds of tissue (cancer tissue versus noncancerous mucosa: 0.34 ± 0.32 versus 0.24 ± 0.27, P = 0.121).

Conclusions: This is the first comprehensive survey of 39 HOX gene expression in ESCC and noncancerous mucosa. Five of the 39 HOX genes were expressed in both types of tissue indicating their possible role in maintaining normal structure and function of adult esophageal mucosa. Eleven of the 39 HOX genes were deregulated in cancer tissue. These genes possibly participate in the carcinogenesis of ESCC.

Key Words: HOX gene network • Esophagus • Epithelium • Carcinoma

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