PURPOSE: The present study investigated the clinical significance of secreted protein, acidic and rich in cysteine (SPARC), in the development and progression of gastric cancer. EXPERIMENTAL DESIGN: Immunohistochemistry was used to analyze SPARC, integrin beta1, and matrix metalloproteinase (MMP)-2 expression in 436 clinicopathologically characterized gastric cancer cases. RESULTS: SPARC, integrin beta1, and MMP-2 protein levels were upregulated in gastric cancer lesions compared with adjacent noncancerous tissues. SPARC protein was detected in 334 of 436 human gastric cancer cases and was highly expressed in 239 tumors. We also found a positive correlation between expression of SPARC and MMP2, and SPARC and integrin beta1. In stages I, II, and III, the 5-year survival rate of patients with a high expression of SPARC was significantly lower than those in patients with low expression. In stage IV, SPARC expression did not correlate with the 5-year survival rate. Further multivariate analysis suggested that the depth of invasion; lymph node and distant metastasis; tumor-node-metastasis stage; and upregulation of SPARC, MMP-2, and integrin beta1, were independent prognostic indicators for the disease. CONCLUSIONS: Our study provided a basis for the development of a novel biomarker for diagnosis and prognosis of gastric cancer. Expression of SPARC in gastric cancer is significantly associated with lymph node and distant metastasis, high MMP2 expression, high intergrin beta1 expression, and poor prognosis. SPARC, intergrin beta1, and MMP-2 protein could be useful markers to predict tumor progression.
PURPOSE: The present study investigated the clinical significance of secreted protein, acidic and rich in cysteine (SPARC), in the development and progression of gastric cancer. EXPERIMENTAL DESIGN: Immunohistochemistry was used to analyze SPARC, integrin beta1, and matrix metalloproteinase (MMP)-2 expression in 436 clinicopathologically characterized gastric cancer cases. RESULTS:SPARC, integrin beta1, and MMP-2 protein levels were upregulated in gastric cancer lesions compared with adjacent noncancerous tissues. SPARC protein was detected in 334 of 436 humangastric cancer cases and was highly expressed in 239 tumors. We also found a positive correlation between expression of SPARC and MMP2, and SPARC and integrin beta1. In stages I, II, and III, the 5-year survival rate of patients with a high expression of SPARC was significantly lower than those in patients with low expression. In stage IV, SPARC expression did not correlate with the 5-year survival rate. Further multivariate analysis suggested that the depth of invasion; lymph node and distant metastasis; tumor-node-metastasis stage; and upregulation of SPARC, MMP-2, and integrin beta1, were independent prognostic indicators for the disease. CONCLUSIONS: Our study provided a basis for the development of a novel biomarker for diagnosis and prognosis of gastric cancer. Expression of SPARC in gastric cancer is significantly associated with lymph node and distant metastasis, high MMP2 expression, high intergrin beta1 expression, and poor prognosis. SPARC, intergrin beta1, and MMP-2 protein could be useful markers to predict tumor progression.
Authors: Agnieszka K Witkiewicz; Boris Freydin; Inna Chervoneva; Magdalena Potoczek; Wendy Rizzo; Hallgeir Rui; Jonathan R Brody; Gordon F Schwartz; Michael P Lisanti Journal: Cancer Biol Ther Date: 2010-08-21 Impact factor: 4.742