Expression of MDA-7/IL-24 and its clinical significance in resected non-small cell lung cancer.
OBJECTIVE
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.


METHODS
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.
Ishikawa
Shinya
S
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Shogoin-kawahara-cho 54, Sakyo-ku, Kyoto 606-8507.
Nakagawa
Tatsuo
T
Miyahara
Ryo
R
Kawano
Yozo
Y
Takenaka
Kazumasa
K
Yanagihara
Kazuhiro
K
Otake
Yosuke
Y
Katakura
Hiromichi
H
Wada
Hiromi
H
Tanaka
Fumihiro
F
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D017209:Apoptosis; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007378:Interleukins / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24