Osteopontin expression is an independent adverse prognostic factor in resectable gastrointestinal stromal tumor and its interaction with CD44 promotes tumor proliferation

Background: Osteopontin (OPN) is a multifunctional secreted glycophosphoprotein involved in miscellaneous physiologic and pathologic processes and is functionally related to the transmembrane receptor CD44. Although OPN expression has been identified to be associated with poor prognosis in several gastrointestinal malignancies, its expression in gastrointestinal stromal tumor (GIST) has not been thoroughly investigated. This study was designed to evaluate the clinicopathologic significance of OPN expression in patients with resectable GIST. Methods: OPN expression was analyzed for its clinicopathologic significance in surgical specimens from 99 patients with resectable GIST by immunohistochemistry. In situ Proximity Ligation Assay was used for examining OPN and CD44 interaction in tumor tissues and GIST cell lines. The in vitro effects of OPN and its interaction with CD44 also were assessed. Results: Increased OPN expression was a significant poor prognostic factor that independently predicted recurrence and poor disease-free survival in patients with resectable GIST. The interaction of OPN and CD44 was confirmed by their significant correlation in both GIST tumor tissues and cell lines by in situ Proximity Ligation Assay analysis. OPN and its interaction with CD44 were related to increased mitosis and significantly enhanced GIST tumor cell proliferation in vitro. Conclusions: Our study identified the clinicopathologic significance and biologic effects of OPN expression in resectable GIST. Increased OPN expression was an independent poor prognostic factor and its interaction with CD44 significantly correlated with increased mitosis as well as in vitro proliferation-promoting effects.