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.
Hsu
Kai-Hsi
KH
Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Tsai
Hung-Wen
HW
Lin
Pin-Wen
PW
Hsu
Yun-Shang
YS
Shan
Yan-Shen
YS
Lu
Pei-Jung
PJ
D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007414:Intestinal Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism*; D016019:Survival Analysis
D018960:Hyaluronan Receptors; D053495:Osteopontin