Clinical Significance of the Loss of KiSS-1 and Orphan G-Protein–Coupled Receptor ( hOT7T175 ) Gene Expression in Esophageal Squamous Cell Carcinoma

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Abstract
Purpose: Lymph node metastasis is the most important predictor of prognosis in esophageal squamous cell carcinoma (ESCC). Recently, KiSS-1 was cloned as a human metastasis suppressor gene, and an orphan G-protein-coupled receptor (hOT7T175) was identified as the endogenous receptor of the KiSS-1 product. However, the clinical importance of KiSS-1 and hOT7T175 gene expression in ESCC remains unclear. Experimental Design: In this study, total RNA was extracted from tumors and noncancerous epithelia of 71 patients with ESCC who underwent surgical esophageal resection. The expression levels of KiSS-1, hOT7T175, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were analyzed quantitatively by real-time reverse transcription-PCR and compared with the clinical findings. Results: The mean KiSS-1:GAPDH and hOT7T175:GAPDH ratios of the tumors were 1.2 and 0.3 and were at the same levels as those in the noncancerous epithelia. The loss of KiSS-1 and hOT7T175 gene expression was detected in 38% and 61% of tumors. Loss of KiSS-1 and/or hOT7T175 gene expression was not correlated with tumor size or degree of tumor invasion but was found to be a significant predictor of lymph node metastasis. Conclusions: Loss of KiSS-1 or hOT7T175 gene expression may be an important biomarker for detection of lymph node metastasis in ESCC.

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