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Extranodal Nasal-type NK/T-cell Lymphoma:the Expression And Significance Of MTOR、4E-BP1、MMP-26 And TIMP-4

Posted on:2016-12-22Degree:MasterType:Thesis
Country:ChinaCandidate:Q ZhangFull Text:PDF
GTID:2284330503951826Subject:Otorhinolaryngology
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Objective: Extranodal Nasal-type NK/T-cell Lymphoma(ENKCL) is a kind of refractory type of the non-hodgkin’s lymphomas(NHLs). It is highly aggressive and the corresponding mortality is high, which is not sensitive to chemotherapy. At present, we did not know the exact pathogenesis of ENKCL. So in this study, we proposed that mTOR/EBP1 signal pathway and the invasion and metastasis of tumor is still the key mechanism which lead to the occurrence of ENKCL. Accordingly, MMP-26、TIMP-4、mTOR and 4E-BP1 were selected to our study, we would use immunohistochemistery method to detect the expression of these 4 markers in the Nasal NK/T cell lymphoma and the control benign reactively hyperplasic lymph tissue. We hope we can find role of these 4 markers in the development of Nasal NK/T cell lymphoma, and try to provide some information for the future clinical target treatment and individual treatment for ENKCL.Method: The study samples were collected from the pathology department of the Huanhu Hospital of Tianjin. We have collected 36 cases of ENKCL, including sorting clinical stage, general condition score and international prognostic index(IPI). They are 27 male cases and 9 female cases. The ages of the patient were between 25-72 y.o. The median age is 51 y.o. 20 cases of adenoid hypertrophy tissue were selected as the control. There was no significant difference between the two groups. All specimens were stained by K8000,the immunohistochemical staining method. Effectiveness of the predictive value of MMP-26, TIMP-4, mTOR and 4E-BP1 proteins expression in ENKCL were estimated by comparing the sensitivity, specificity and Youden’s indx.Count data was analysis by χ2 test.The method of pearson contingency coefficine was used to analysis the correlation.Calculations were performed by SPSS seventeen statistical software for windows, with level of two-sided test. P<0.05 to determine significant differences.Results:1. The positive expression rate of MMP-26 in adenoid hypertrophy cases and ENKCL were 55.6% and 20.0% respectively,and the difference is statistically significant( χ2 = 6.637,p=0.01); 2.The positive expression rate of TIMP-4 in adenoid hypertrophy cases in ENKCL and 20 cases of were 38.9% and 5.0% respectively, the difference is statistically significant(χ2=7.529,p=0.006); 3.The positive expression rate of mTOR in adenoid hypertrophy cases in ENKCL and 20 cases of were 63.9% and 15.0% respectively,and the difference is statistically significant(χ2= 12.355,p=0.0001); 4.The positive expression rate of 4E-BP1 lymph node reactive lymphoid hyperplasia cases in 36 patients and 20 cases of were 58.3% and 10.0% respectively, the difference is statistically significant(χ2=12.410,p=0.0001);5.In the prognostic analysis of ENKCL, we found that in ENKCL,the expression of MMP-26 and 4E-BP1 shows significant correlation with IPI of lymphoma(p=0.027,0.044),and the expression of mTOR shows significant correlation with clinical stages of lymphoma(p=0.0001); 6.1n the correlation analysis,we found that in ENKCL, the expression of mTOR shows significant positive correlation with the expression of MMP-26(r = 0.351,p=0.024),with the expression of 4E-BP1(r = 0.547, p=0.001); 7.The sensitivity, specificity and Youden’s indx analysis showed that the detection of MMP-26 and 4E-BP1 proteins expression may be one better molecular markers to diagnosis the ENKCL.Conclusions:1.The abnormal over-expression of MMP-26、TIMP-4、mTOR and 4E-BP1 proteins had a significant positive correlation with each other in ENKCL,in thus,the positive correlation between the expression of MMP-26 and mTOR,which suggested their correlations with pathogenesis and development of ENKCL; 2.The expression of MMP-26, 4E-BP1 shows significant correlation with IPI of lymphoma and mTOR shows significant correlation with the clinical stages of lymphoma, which could be applied as the biomarker of ENKCL prognosis; 3.The expression of mTOR shows significant positive correlation with the expression of 4E-BP1, suggested that the mTOR、4E-BP1 cooperated through a common signal transduction road to lead to the process of growth, differentiation and metastasis of the ENKCL; 4.The detection of mTOR and p-4EBPl proteins expression was the better molecular markers to predict diagnosis of the ENKCL.
Keywords/Search Tags:Extranodal Nasal-type, NK/T cell lymphoma, adenoid hypertrophy tissue, MMP-26, TIMP-4, mTOR, 4E-BP1
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