| Gastric cancer is one of the most common cancers worldwide. Although a declined incidence has been observed in recent years, in many countries including China, the gastric cancer is still contributed to the highest mortality amongst other cancers. Advances in diagnosis and treatment have offered better long-term survival for early gastric cancer;however, the prognosis of advanced cancer remains poor. Most of the patients with gastric cancer die from tumor invasion, metastases and recurrence rather than the original tumor itself. So it's necessary to search for potential prognostic factors that help to predict the prognosis of the patients, and to give guides for personalized treatment and to enhance long-term survival.Recent knowledge in molecular biology indicates that the invasion and metastasis of tumor is a multigenetic and mutistep progression. Some genes and molecules involved in that progression have been indicated as potential prognostic factors. They are classified to growth factors and their receptors, cell-cycle regulators, telomere, cell-adhesion molecules and matrix-degrading enzymes and including epidermal growth factor (EGF), EGF receptor, K-sam, HER-2, interleukin (IL)-8, vascular endothelial growth factor (VEGF), cyclin E, p27, p53, Ecadherin, CD44v6, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Recently, it has been shown that the overexpression of several genes including RBP4, OCT2, IGF2,PFN2, KIAA1093, OPN, PCOLCE, FN1 etc. is associated with the invasion, metastasis of alimentary tract tumor and prognosis of patients. In this study, we investigated the expressions of OPN, OCT2 correlation with the clinicopathologic features of gastric cancer.Osteopontin (OPN) is a multifunctional phosphoprotein secreted by many cell types including osteoclasts, lymphocytes, macrophages, and tumorcells. It is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, wound healing and tumor metastasis. Recently, OPN has been improved to associate with tumor invasion and metastasis. Some studies revealed that the expression levels of OPN in blood or tumor tissue may provide useful clinical information for cancer bearing patients thus for better prognosis. Although OPN has been demonstrated expressed in a variety of human carcinoma including lung, breast, esophagus, liver and prostate, the molecular mechanisms that define the role of OPN in tumor invasion and metastasis are incompletely understood.The Oct-2 transcription factor is a member of POU family of transcription factors, which was originally identified in B lymphocytes and was named on the basis of its ability to bind to the octamer sequence ATGCAAAT which is present in the promoter and enhancer elements of the immunoglobulin genes. The Oct-2 has been generally regarded as a lymphoid or neuronal cell-specific transcription factor but not expressed by other cell types. In 2002, Yoshitaka et al. observed a strong expression of OCT2 in gastric cancer cells with lymph node metastasis and in some infiltrating lymphocytes, but not in cancer cells without metastasis.Tissue chip (TC), also named tissue microarray (TMA), is a newly developed molecular biologic technology based on cell morphology. It can be used to test gene and protein location in variety of techniques in situ analysis including histochemical staining, immunohistochemical staining ^ immunofluorescent staining, or in situ hybridization. Because tissue microarray technology allows rapid and simultaneous morphological observation of molecular targets in large collectives of tissue specimens under standardized conditions, so we used this technology in our experiments.In this study, tumor tissue specimens were taken from ninety-nine cases gastric cancer patients who operated in the first hospital of Shaoxing between 1995 and 2000. Specimens taken from twenty-five cases of chronic gastritis or gastric ulcer served as control group. The study procedurewere: making of tissue microarray after the carefully checking of medical records and HE slides for clinicopathological features by expert clinical doctors;detecting the mRNA and protein expression levels of OPN and OCT2 by in situ hybridization and immunohistochemistry methods;and the statistic analysis regarding the experiment data, the clinicalpathologic characteristic and the follow-up materials.SPSS 11.5 software was used for statistical analysis. The statistical methods used include %2 test, Spearman rank correlation analysis, Kaplan-Meier survival curve analysis and log rank test. The level of statistical significance was defined as P <0.05.In situ hybridization results indicated that: from the 99 cases, the positive rates of OPN mRNA and OCT2 mRNA expression were 60.61%, 64.65%, respectively;there were significant relationships of OPN mRNA expression with tumor diameterCr = 0.295, P = 0.003), invasion depth (r = 0.289, P = 0.004), vessel invasionCr = 0.437, P = 0.000), lymph node(r = 0.335, P = 0.001) and distant metastasis (r = 0.253, P = 0.011);there were significant relationships of OCT2 mRNA expression with tumor diameter (r = 0.354 , P = 0.000) , invasion depth (r = 0.378, P = 0.000) , vessel invasion (r = 0.348, P = 0.000) , lymph node (r = 0.297, P = 0.003) and distant metastasis (r = 0.253, P = 0.011);there was a positive relationship of OPN mRNA with OCT2 mRNA expression;the mean survival time in OPN mRNA and OCT2 mRNA positive expression cases was significantly shorter than those with OPN and OCT2 mRNA negative expression.Immunohistochemistry results revealed that: from the 99 cases, the positive rates of OPN and OCT2 protein expression were 60.61 %, 54.55 %, respectively;there were significant relationships of OPN protein expression with tumor diameter (r = 0.295 , P = 0.003 ) , invasion depth (r = 0.295, P = 0.003) , vessel invasion (r = 0.395, P = 0.000) , lymph node (r = 0.293, P = 0.003) and distant metastasis (r = 0.235, P = 0.019);there were significant relationships of OCT2 protein expression with tumor diameter (r = 0.352, P = 0.000 ) , invasion depth (r = 0.271, P = 0.007) , vessel invasion (r = 0.325, P = 0.001), lymph node (r = 0.292, P = 0.003)and distant metastasis (r = 0.239, P = 0.017);There was a positive relationship of OPN protein with OCT2 protein expression;the mean survival time in cases with OPN protein and OCT2 protein positive expression was significantly shorter than those without OPN and OCT2 protein expression.In conclusion, this study revealed that OPN and OCT2 might be involved in the growth, invasion and metastasis of gastric cancer cells;the expression patterns of OPN and OCT2 have significant influence on the prognosis of gastric cancer patients;immunostaining for levels of OPN and OCT2 expression by tissue microarray assay can be used as professional prognostic markers and genetic treatment indicators for gastric cancer patients.
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