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IRF8as A Predictive Biomarker For Diffuse Large B-Cell Lymphoma

Posted on:2013-03-12Degree:MasterType:Thesis
Country:ChinaCandidate:H H NiuFull Text:PDF
GTID:2234330362975544Subject:Biochemistry and Molecular Biology
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Objective: Diffuse large B-cell lymphoma (DLBCL) is one of the most common types ofnon-Hondgkin’s lymphoma in adults. Chemotherapy based on DNA-damaged drugs is the majortreatment for this disease. However, it remains elusive to find a predictive biomarker forchemotherapy efficacy for DLBCL. In this study, we examined the expression levels oftranscription factor interferon regulatory factor8(IRF8) in DLBCL, and its usefulness inpredicting patients’ outcome following CHOP-based chemotherapy.Methods: In this thesis, collected a total of113cases of DLBCL clinical samples, including65samples with intact data and follow-up data. In this65DLBCL patients: the44of65(67.7%)patients were male, the21of65(32.3%) patients were female, and the sex ratio was2.1: l. The agerange was from19to83years and the median age was56years. The onset of29(44.6%)patientswere primary lymph nodes; and36(55.4%) patients were primary extranodal organizations. Thisgroup of patients were followed up from1to62months, median follow-up time was21months.In this study, immunohistochemistry method was used to examine the expression levels ofIRF8protein and then the results was assessed by using the manual counting method. On the otherhand, total RNA was extracted from paraffin-embedded tissue of65cases of DLBCL samples andtranscribed into cDNA. And probe based real-time PCR technology was used to compare theexpression of IRF8mRNA in DLBCL patients’ tumor tissue. And then further analyzed therelationship between IRF8protein and mRNA expression levels, respectively, with the overallsurvival time of patients by the Kaplan-Meier estimator and Log-rank test.Results: The expression levels of IRF8were the highest in the germinal center of lymphoidtissue. In those patients treated with CHOP chemotherapy, whose tumor tissue expressed lowerlevels IRF8mRNA had longer overall survival time. The levels of IRF8mRNA were significantlyassociated with DLBCL patients’ overall survival time (P<0.05). The levels of IRF8protein didshow a trend to correlate with patients’ survival, though it did not reach a statistical significance (P=0.094). Conclusion: This study was the first to find that the IRF8gene expression level in the tumortissue of DLBCL was highly correlated with patient’s overall survival. Patients with higher level ofIRF8mRNA had shorter survival time than those with lower levels of IRF8mRNA.
Keywords/Search Tags:diffuse large B cell lymphoma, molecular marker, prognosis, interferonregulatory factor8
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