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Endogenous Secretory Receptor for Advanced Glycation End Products in Non–Small Cell Lung Carcinoma

Departments of Geriatric and Respiratory Medicine, and Department of Pathology, Tohoku University School of Medicine; Department of Thoracic Surgery, Institute of Development, Aging, and Cancer, Tohoku University; Sendai Kousei Hospital, Sendai; and Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

Correspondence and requests for reprints should be addressed to Hiroshi Kubo, M.D., Ph.D., Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryoumachi, Aobaku, Sendai 980-8574, Japan. E-mail: hkubo{at}geriat.med.tohoku.ac.jp

Rationale: The receptor for advanced glycation end products is a multiligand receptor that plays an important role in regulating the invasiveness and metastatic potential of cancer cells. A recently discovered novel splice variant, the endogenous secretory receptor for advanced glycation end products, mediates the receptor for advanced glycation end-product–associated cell responses by functioning as a decoy receptor.

Objectives: To evaluate the expression pattern of endogenous secretory receptor for advanced glycation end products in non–small cell lung carcinoma, and analyze its impact on prognosis.

Methods: We performed immunohistochemical evaluation in 182 non–small cell lung carcinoma surgical specimens. The effect of an overexpressed receptor in cancer cell proliferation was also evaluated.

Measurements and Main Results: The endogenous secretory receptor for advanced glycation end-product expression in cytoplasm was reduced or absent in 137 of the 182 (75%) carcinomas in contrast to normal lung tissues. mRNA expression was also suppressed in cancer cells. Overexpression of the secretory receptor in lung cancer cell lines had an inhibitory effect on cell proliferation, suggesting the reduced receptor expression accelerated tumor growth. Among patients with low expression of the cytoplasmic secretory receptor, the overall survival rate was significantly lower than that of patients with normal expression (p = 0.0003). This association was most prominent in TNM stage I patients (p = 0.0001). In a multivariate analysis, endogenous secretory receptor immunoreactivity was an independent prognostic factor with a relative risk of 3.1.

Conclusions: The cytoplasmic endogenous secretory receptor for advanced glycation end-product expression has the potential to be a prognostic factor for predicting the outcome of curative surgery in patients with non–small cell lung carcinoma.

Key Words: clinical study • lung cancer • prognostic factor • receptor • surgery

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Recent trials of adjuvant chemotherapy in patients with completely resected lung cancer have demonstrated an improved outcome over surgery alone. However, there is no prognostic factor to identify patients most likely to benefit from chemotherapy. What This Study Adds to the Field Determining expression levels of cytoplasmic endogenous secretory receptor for advanced glycation end-product has the potential to characterize prognosis in patients with non–small cell lung cancer.

 

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