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Expression of MDA-7/IL-24 and Its Clinical Significance in Resected Non–Small Cell Lung Cancer

¹ Department of Thoracic Surgery, Faculty of Medicine, Kyoto University; ² Department of Translational Clinical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; and ³ Department of Thoracic Surgery, Seishin-Iryo Center Hospital, Kobe, Japan

Requests for reprints: Fumihiro Tanaka, Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Shogoin-kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 75-751-4975; Fax: 75-751-4974; E-mail: ftanaka{at}kuhp.kyoto-u.ac.jp.

Purpose: The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin (IL)-24, is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells including lung cancer cells. However, only one clinical study has documented that MDA-7/IL-24 expression is down-regulated with progression of melanoma. Thus, the present study was conducted to assess the clinical significance of MDA-7/IL-24 expression in non–small cell lung cancer.

Experimental Design: A total of 183 consecutive patients with resected pathologic stage I-IIIA, non–small cell lung cancer were retrospectively reviewed, and immunohistochemical staining was used to detect MDA-7/IL-24 expression.

Results: MDA-7/IL-24 expression was high in 97 (53.0%) patients and low in the other patients. There was no significant correlation between MDA-7/IL-24 status and any patients' characteristic including pathologic stage. There was no significant difference in tumor angiogenesis or proliferative activity according to MDA-7/IL-24 status, but MDA-7/IL-24-high adenocarcinoma showed a significantly higher incidence of apoptotic tumor cell death than MDA-7/IL-24-low adenocarcinoma. MDA-7/IL-24-high patients seemed to show a favorable postoperative prognosis as compared with MDA-7/IL-24-low patients (5-year survival rates, 75.9% and 62.0%, respectively), although the difference did not reach a statistical significance (P = 0.061). Subset analyses showed that positive MDA-7/IL-24 expression was a significant factor to predict a favorable prognosis in adenocarcinoma (P = 0.033), which was confirmed by a multivariate analysis; there was no difference in the prognosis according to MDA-7/IL-24 status in squamous cell carcinoma.

Conclusions: MDA-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma.

Key Words: Melanoma differentiation associated gene-7 • MDA-7 • IL-24 • Lung cancer • Surgery • Prognosis

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