Prognostic Significance of Osteopontin Expression in Human Gastric Carcinoma

Abstract

Osteopontin (OPN) is a secreted, integrin-binding glycophosphoprotein that has been implicated in the progression of various solid tumors. To evaluate the clinical significance of OPN in gastric carcinoma, we investigated OPN expression in resected tumors. Expression of OPN protein by gastric cancer cells was evaluated using western blot analysis. OPN messenger RNA (mRNA) expression in 18 gastric cancers was compared with that in the corresponding normal gastric epithelium by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Paraffin sections of tumors from 295 patients with gastric cancer were also investigated using immunohistochemistry. All four gastric cancer cell lines analyzed using western blotting had almost the same level of OPN protein expression as the positive control (HeLa cells). OPN mRNA was upregulated in 83% (15/18) of the tumors studied. On immunohistochemical staining, 90 tumors were classified as negative (-), whereas 205 were classified as positive (1+, 2+, or 3+). The level of OPN protein expression was significantly associated with the patient's age (p = 0.04), tumor depth (p = 0.03), histological grade (p = 0.008), and hematogenous metastasis (p = 0.007). Kaplan-Meier analysis showed that OPN positivity was significantly associated with a shorter survival time (p = 0.027). Furthermore, multivariate analysis revealed that OPN positivity was an independent risk factor for hematogenous metastasis (p = 0.034). The present findings suggest that increased tumor expression of OPN is an important determinant of shorter survival time and that OPN positivity may be useful for predicting the risk of hematogenous metastasis in gastric cancer patients.