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Expression And Clinical Significance Of BCL-2 And NF-κB/p65 In Diffuse Large B-cell Lymphoma

Posted on:2008-04-21Degree:MasterType:Thesis
Country:ChinaCandidate:Z L HuangFull Text:PDF
GTID:2144360218454153Subject:Oncology
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Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma, characterized by marked clinical and biologic heterogeneity and different prognosis.It is particularly needed to make the search for prognostic factors/biomarkers identifying patients at high risk, which is favourable for predicting patients and guiding personalized therapy.The clinical prognostic factors described in the International Prognostic Index (IPI) have been used in risk stratification for patients with diffuse large B-cell lymphoma (DLBCL) for more than a decade. Although the IPI has proved valuable for stratification of patients in clinical application, there is prognostic variability in the same risk groups. Additionally, there is little evidence that therapy tailored to specific IPI risk groups have improved outcome, making the insufficiency of IPI clear.The failure of these clinical risk factors to exactly predict response to specific therapies reflects the inherent biological heterogeneity, among which the alteration of apoptosis-related genes or their expression make it especially clear. Additionally, anticancer drug-induced apoptosis in killing cancer cells plays an important role in drug treatment of malignant lymphoma.The effects of antitumor drugs will change inevitably if apoptosis-related genes alter in malignant lymphoma. Thus, the investigation of inherent biological heterogeneity of apoptosis-related genes expression in diffuse large B-cell lymphoma may have important significance on risk stratification and predicting response to specific therapies for patients with diffuse large B-cell lymphoma. Objective: To investigate the correlation between apoptosis-related genes alteration and response to chemotherapy and prognosis of malignant lymphoma,and in particular,to investigate the expression and clinical significance of BCL-2 and NF-κB/p65 in diffuse large B-cell lymphoma.To predict the effect of anticancer drugs,and to provide help for prognosing and selecting anticancer agents and guiding individual therapy.Method: A total of 31 patients with diffuse large B-cell lymphoma treated in the First Affiliated Hospital of Anhui Medical University were investigated. Formalin–fixed, paraffin-embedded sections were analyzed for the expression of BCL-2 and NF-κB/p65 protein by immunohistochemistry.Results: The rate of positivity of BCL-2 and NF-κB/p65 proteins in diffuse large B-cell lymphoma patients was 51.6% and 38.7% respectively, with significant correlation between them. The expressions of BCL-2 and NF-κB /p65 protiens had relationship with the patients'Ann Arbor stage, response to chemotherapy and survival;but not with the patients'age, gender and IPI. Such expressions were higher in diffuse large B-cell lymphoma patients with Ann Arbor stageⅢ/Ⅳand poor response to chemotherapy and survival. Diffuse large B-cell lymphoma patients with B symptoms showed significantly higher NF-κB/p65 expression, but no higher BCL-2 expression than those without B symptoms.Conclusion:There may be relationships between the expression of BCL-2 and NF-κB proteins and the clinical features and prognosis, so these expressions may define a group of diffuse large B-cell lymphoma patients with a poor prognosis, and could be used as reference biomarkers to predict poor response to chemotherapy and survival and is helpful in guiding personalized therapy and finding new therapy target.
Keywords/Search Tags:Bcl-2, NF-kappaB, Apoptosis, lymphoma,diffuse,B-cell, Drug therapy, Prognosis
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