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Hepatoma-derived Growth Factor Is Associated with Reduced Sensitivity to Irradiation in Esophageal Cancer

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan [A. M., H. I., K. S., M. M.]; Department of Surgery, Saitama Prefectural Cancer Center, Saitama 362-0806, Japan [Y. T.]; Department of Medicine, Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01655 [G. F. B.]; and Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan [K. S.]

Radiotherapy is a useful component of treatment for esophageal cancer. Identification of the genes that are differentially expressed between radiosensitive and radioresistant cancer cells is important for predicting clinical effectiveness of radiotherapy. We established human esophageal cancer cell lines resistant to X-ray. Using differential display, we obtained one gene that was expressed in radiosensitive cells but was rarely expressed in radioresistant cells, and that gene was identical with hepatoma-derived growth factor (HDGF), an acidic polypeptide with mitogenic activity for fibroblasts. The semiquantitative reverse transcription-PCR assay confirmed that HDGF mRNA expression was reduced in established radioresistant cells, and its reduction was associated with reduced sensitivity to irradiation. Radiotherapy was more effective in clinical cases with high HDGF mRNA expression compared with cases with low expression (P < 0.05). The findings demonstrate that HDGF may play an important role in radiosensitivity, and it could be a novel marker predicting effectiveness of radiotherapy in clinical cases.

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