SPARC Is Associated with Gastric Cancer Progression and Poor Survival of Patients

Abstract

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 β1, and matrix metalloproteinase (MMP)-2 expression in 436 clinicopathologically characterized gastric cancer cases.Results: SPARC, integrin β1, 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 β1. 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; tumornode-metastasis stage; and upregulation of SPARC, MMP-2, and integrin β1, 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 β1 expression, and poor prognosis. SPARC, intergrin β1, and MMP-2 protein could be useful markers to predict tumor progression.

MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis

“…MiR-125b is a small, noncoding, multipurpose RNA molecule. It is one of the first MiRNAs to be identified, and it plays a key role in several processes in many kinds of cells, such as the control of cell proliferation, differentiation, and apoptosis [12][13][14][15]. The expression of MiR-125b in cancers is controversial.…”

“…Digoxin-labeled MiR-125b probe (MiRCURY LNA Detection Probe, 250 pmol, 3 0 -DIG labeled, Exiqon, Copenhagen, Denmark) was used to detect cytoplasmic MiR-125b. The degree of immunostaining was reviewed and scored independently by 2 observers based on the proportion of positively stained tumor cells and stain intensity [11,12]. Tumor cell proportion was scored as follows: 0 (B5 % positive tumor cells), 1 (6-25 % positive tumor cells), 2 (26-50 % positive tumor cells), and 3 ([51 % positive tumor cells).…”

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

“…cancer including hepato-cellular carcinoma , colorectal cancer and gastric cancer (Zhao et al, 2010). It also has been reported that MMP12 correlates with metastasis in hepatocellular carcinoma (Ng et al, 2011), squamous cell carcinoma (Kerkerla et al, 2002) and non-small cell lung cancer (Hofmann et al, 2005).…”

Clinical significance of secreted protein, acidic and cysteine-rich gene expression in patients with stage II/III gastric cancer following curative resection and adjuvant chemotherapy with S-1

“…Infante et al (23) reported that patients whose pancreatic cancer stroma expressed SPARC exhibited a significantly poorer outcome than patients whose tumor stroma did not express SPARC. Zhao et al (16) also reported that high SPARC expression was significantly associated with poorer 5-year Figure 6. Comparison of overall survival rates between low and high SPARC expression levels in patients who had following adjuvant S-1 chemotherapy (P=0.000006, as determined using the log-rank test).…”

“…SPARC expression is upregulated in many types of cancer (9), including pancreatic cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer and gliomas (7,(10)(11)(12)(13)(14)(15). SPARC expression is also associated with patient outcomes and clinicopathological features, including the depth of cancer cell invasion and metastasis (16,17).…”