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Relationship Between Prognosis And Expressions Of Galectin-9and MMP-2 Proteins In Esophageal Squamous Cell Carcinoma

Posted on:2013-11-05Degree:MasterType:Thesis
Country:ChinaCandidate:S P GuoFull Text:PDF
GTID:2234330371976968Subject:Internal Medicine
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Backgroud and purposeEsophagus carcinoma is a common malignant tumors of the world some countries and regions. in the Middle East,Africa, and Asia, and parts of Europe, squamous cell esophageal cancer (SCCE) dominates the esophageal cancer landscape. World-wide rates are highest in Northern China, South Africa, Turkey, and Iran.In the United States, the black population has a five-fold higher incidence of SCCE than the white population,83% percent of blacks with esophageal cancer present with SCCE. The cause of esophagus carcinoma is still unclear. The best known and accepted risk factors for SCCE include a constellation of factors at the population, individual, and cellular level, including though not limited to race, socioeconomic class, diets low in fruits in vegetables, achalasia, systemic sclerosis, previous esophageal stricture, and a prior history of squamous cell tumors of the head and neck or lung. In China, risk factors are similar but also include diets high in N-nitroso compounds, fungal toxins, diets low in selenium and zinc, highly salted meats, and diets with low intake of vitamins A and C and the consumption of very hot beverages. Progress has also been made in identifying the molecular alterations that lead to esophageal cancers. These include functional losses of tumor suppressor genes, For the most part, these functional losses are induced by loss of heterozygosity (LOH) and, to a lesser degree, by methylation changes or by mutational changes in these genes that inhibit apoptosis or act as breaks at crucial phases within the cell cycle.Cyclins, especially cyclin D1 and cyclin E, are almost always upregulated in esophageal cancers. But its specific moleeular meehanism is unclear.Previous studies have shown that:the galectin-9 are widely distributed in the islet cells of human tissue, liver, lung, stomach, brain, breast, uterus, tonsil, and a variety of immune cells, and expression of galectin-9 natural antibodies in human serum. Galectin-9 is a cytoplasmic protein, targeting secreted into the cytoplasm and the nucleus, interaction with the protein in the cytoplasm and the nucleus, conductivity cell signaling. Galectin-9 induced eosinophil accumulation and activation, regulation of immune and inflammatory responses, and guide tumor cells to evade immune surveillance, while in mediating cell proliferation, differentiation, mature, apoptosis and cell adhesion, aggregation and tumor metastasis play an important role.The relationship between MMP-2 and the tumor is well known, but the study of the relationship between MMP-2 and galectin-9 is relatively small. We have found that galectin-7 induced the expression of MMP-9, Although the identity of the galectin-7 ligand is currently unknown, one could envisage that other galectins could also induce MMP genes. Further investigations will be necessary to examine this possibility by examining the repertoire of galectins. Because members of the galectin family have been shown to be cleaved by members of the MMP family or to modulate their proteolytic activation, our results open a new window from which we can view the functional relationship between the galectins and MMPs during different biological processes, such as neoplastic progression. Material and methods1. Tissue samPles:The establishment of tissue microarray of 63 cases of specimens were from Henan Tumor Hospital thoracic surgery in November 2005 to February 2008 patients with esophageal squamous cell carcinoma surgery, all specimens including cancerous tissue and paired adjacent normal tissue (away from the cutting edge of> 5cm)all specimens were only six cases tumor<3cm. 2. Method:Expressions of Galectin-9 and MMP-2 proteins in 63 cases of ESCC and adjacent non-tumor tissues were detected by using tissue microarray and immunohistochemical technique. The correlations of Galectin-9 and MMP-2 protein expressions with clinicopathologic data and survival were analyzed.ResultsThe positive rate of Galectin-9 protein in adjacent non-tumor tissues and ESCC were 89.3% and 60.3%, respectively (P<0.001). In ESCC, its expression was correlated with prognosis and tumor differentiation (P=0.001). The patients with Galectin-9 positive expression had a longer survival period (P=0.013), and Galectin-9 protein was a significant prognostic factor in ESCC (P=0.029, RR=0.559). The positive rate of MMP-2 protein in adjacent non-tumor tissues and ESCC were 65.1% and 35.7%, respectively (p=0.001). In ESCC, the expression of MMP-2 was correlated with tumor invasion, lymph node metastasis, clinical stage and prognosis, and patients with MMP-2 positive expression showed a shorter survival period. Negative expression of Galectin-9 and positive expression of MMP-2 had a bad prognosis. ConclusionsIn ESCC, the Galectin-9 protein was down-regulated and MMP-2 up-regulated. Combination of Galectin-9 and MMP-2 protein expressions could be markers for prognostic diagnosis in ESCC.
Keywords/Search Tags:Esophagus squamous cell carcinoma, Tissue microarray, Immunohistochemistry, Galectin-9, MMP-2
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