Elevated plasma osteopontin associated with gastric cancer development, invasion and survival

Chun-Ying Wu ¹, Ming-Shiang Wu ², En-Pei Chiang ³, Cheng-Chung Wu ⁴, Yi-Ju Chen ⁵, Chien-Jen Chen ⁶, Nai-Hui Chi ¹, Gran-Hum Chen ¹ and JAW-TOWN LIN ^7*

¹ Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan
² Department of Internal Medicine, National Taiwan University Hospital, Taiwan
³ Department Food Science and Biotechnology, National Chung Hsing University, Taiwan
⁴ Department of Surgery, Taichung Veterans General Hospital, Taiwan
⁵ Department of Dermatology, Taichung Veterans General Hospital, Taiwan
⁶ Institute of Epidemiology, College of Public Health, National Taiwan University, Taiwan
⁷ National Taiwan University Hospital, Taiwan

^* To whom correspondence should be addressed. E-mail: jawtown{at}ha.mc.ntu.edu.tw.

Accepted 29 October 2006

Abstract

Objective: Osteopontin (OPN) has been found valuable in diagnosis and predicting the prognosis of a variety of malignancies. The aims of the present study are to evaluate the usefulness of plasma OPN level for predicting gastric cancer development, invasion and survival.

Patients and Methods: One hundred and thirty-two gastric cancer patients and 93 healthy controls were enrolled. Real-time quantitative RT-PCR and immunohistochemical staining were used to detect OPN expression in gastric cancer tissues. Plasma levels of OPN were measured on ELISA assay. Plasma OPN levels were compared with gastric cancer development, clinicopathological features and outcomes.

Results: OPN mRNA expression was significantly higher in gastric cancer tissues when compared with non-tumor tissues. Most OPN immunoactivity was localized to cancer cells. The median plasma OPN level was significantly higher in patients than in controls (p<0.0001), and significantly higher in patients with advanced stages, serosal invasion, lymph node metastasis, lymphatic invasion, venous invasion, and liver metastasis. Logistic regression analyses showed that high plasma OPN level (>67.3 ng/mL) is significantly associated with advanced stages, serosal invasion, lymph node metastasis, lymphatic invasion, venous invasion and liver metastasis. Plasma OPN level demonstrated significant association with patient survival (p<0.0001), especially in the subgroups with invasive phenotypes. On Cox multivariate analysis, elevated plasma OPN level was an independent risk factor for poor survival (p<0.0001).

Conclusions: Elevated plasma OPN level is significantly associated with gastric cancer development, invasive phenotypes and survival. Plasma OPN level may have potential usefulness as a diagnostic and prognostic factor for gastric cancer.

Keywords: gastric cancer, invasion, osteopontin, plasma, survival

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