| Objective: The Eph receptor tyrosine kinases and their ephrin ligandshave intriguing expression patterns in cancer cells and tumor blood vessels,which suggest important roles for their bidirectional signals in multipleaspects of cancer development and progression. Eph gene mutations likelyalso contribute to cancer pathogenesis. Eph receptors and ephrins have beenshown to affect the growth and migration/invasion of cancer cells in culture aswell as tumor growth, invasiveness, angiogenesis, and metastasis in vivo.However, Eph signaling activities in cancer appear to be very complex, andare characterized by puzzling dichotomies. The Eph receptors neverthelessrepresent promising new therapeutic targets in cancer.Tyrosine kinases, which are the major regulators of signal transductionpathways, are associated with cellular proliferation, apoptosis, andtumorigenesis. The Eph receptor family is the largest subgroup of RTKs. Ephreceptor tyrosine kinases and their membraneanchored ephrin ligands form acell-cell system that is associated with cell-to-cell adhesion ormigration,angiogenesis, and tumor vasculature in various human carcinomas. EphA3isan important member of the Ephs. Nowadays, it has been reported that EphA3is overexpressed in a range of tumors, such as hepatic cancer, lung cancer,renal cancer, melanoma and colorectal cancer, and associated with poorprognosis. In this research, first, we’ll explor the expression of EphA3ingastric cancer. Second, we will investigate the relationship between theEphA3receptor and MMP-2protein and their roles in the angiogenesis ofgastric cancer. At last, survival analysises will be gaven to the patients.Methods: According to the inclusion criteria and the exclusion criteria, atotal of74cases of gastric cancer patients, who were treated in North China Oilfield Hospital between2003to August18,2008, and another16cases ofnormal control patients were collected. Then, it was the collection of clinicalinformation, including age, gender, histological type, degree of differentiation,vascular tumor thrombus, the depth of invasion, lymph node metastasis anddistant metastasis. The follow-up period was calculated from the date ofsurgery until December31th,2012. The expression of EphA3receptor,MMP-2protein and CD34protein in the tumor tissues and the normal controlgroup were detected by immunohistochemical method. SPSS V.13.0was usedfor the statistical analysis. The Pearson χ2test was used to examine variousclinicopathological characteristics associated with the expression of EphA3receptor and MMP-2protein. Data for the microvessel density is presented asmean±SD. T-test and the analysis of variance were used to examine variousclinicopathological characteristics associated with MVD. Two variables usedSpearman rank correlation to analyze. Survival analysises used Kaplan-Meieranalysis and Log-rank method test. A value of P<0.05was consideredstatistically significant.Results:1The positive expression rate of EphA3receptor in patients with gastriccancer was51.35%(38/74), while only18.75%(3/16) in the control group.The expression of EphA3receptor in the gastric cancer group wassignificantly higher than the control group (P<0.05). The positive expressionrate of MMP-2protein in patients with gastric cancer was75.68%(56/74),while only just about12.5%in the control group (2/16). The expression ofMMP-2protein in the gastric cancer group was significantly higher than thecontrol group (P<0.05).2The expression of MMP-2protein in the patients of gastric cancerassociated with histological types, degrees of differentiation, depthes ofinvasion, lymph nodes metastasis and stages (P<0.05), while EphA3associated with the different histological types, degrees of differentiation,depthes of invasion, distant metastasis and stages (P<0.05).3In this rasearch, MVD in the gastric cancer patients was significantly higher than the control group (P<0.05), which maximum value was85.2,minimum14.4and average of41.59±15.021in the gastric cancer group whilemaximum48.2, minimum12.0and a mean of21.75±9.270in the controlgroup.4In this study, MVD in the gastric cancer patients significantlyassociated with histological types, tumor differentiations, depthes of tumorinvasion, lymph nodes metastasis, distant metastasis and TNM stages(P<0.05).5In the gastric cancer patients, the mean of MVD in the positiveexpression of MMP-2protein group was46.30±13.896, which was51.97±12.249in the positive expression of EphA3receptor group. MVD inthe positive and negative expression group of EphA3receptors and MMP-2protein were significantly different (P<0.05).6In this study, we defined MVD≥30as MVD high expression groupwhile MVD<30as the low expression group. Then, we found the expressionof EphA3positively correlated with MMP-2protein and MVD (P<0.05).7Survival analysis showed that the survival times of patients between thedifferent histological types, degrees of differentiation, vascular invasion,depthes of tumor invasion, lymph nodes metastasis, distant metastasis andstages were significant difference (P<0.05). The patients of positiveexpression of EphA3receptor, MMP-2protein or MVD lived shorter than lowexpression (P<0.05).Conclusions:1The expression of EphA3receptor and MMP-2protein in gastric cancertissues significantly increased compared with the normal gastric mucosaes.EphA3receptor and MMP-2protein involved in gastric carcinogenesis and theprogression of gastric cancer. Also, they may be potential indicator for clinicalassessment of tumor prognosis.2MVD in gastric cancer tissues than the normal gastric mucosaesincreased, suggesting that angiogenesis play an important role in gastriccancer development, distant metastasis, even poor prognosis of patients. 3EphA3receptor and MMP-2protein played important roles in gastriccancer angiogenesis, and promoted the progresssion and metastasis of gastriccancer. |
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