Biomarker identification in HIV and non-HIV related lymphomas

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dc.contributor.advisorNaidoo, Richarden_ZA
dc.contributor.advisorGovender, Dhirenen_ZA
dc.contributor.authorMagangane, Pumza Samanthaen_ZA
dc.date.accessioned2017-01-19T12:22:29Z
dc.date.available2017-01-19T12:22:29Z
dc.date.issued2016en_ZA
dc.description.abstractDLBCL is the most common lymphoma subtype occurring in older populations as well as in younger HIV infected patients. The current treatment options for DLBCL are effective for most patients yet the relapse rate is high. While many biomarkers for DLBCL exist, they are not in clinical use due to low sensitivity and specificity. In addition, these biomarkers have not been studied in the HIV context. Therefore, the identification of new biomarkers for HIV negative and HIV positive DLBCL, may lead to a better understanding of the disease pathology and better therapeutic design. Initially differences in the clinicopathological features between HIV negative and HIV positive DLBCL patients were determined by conducting a retrospective study of patients treated at GSH. Subsequent to this, potential protein biomarkers for DLBCL were determined using MALDI imaging mass spectrometry (IMS) and characterised using LCMS. The expression of one of the biomarkers, heat shock protein (Hsp) 70, was confirmed on a separate cohort of samples using immunohistochemistry. Our results indicate that the clinicopathological features for HIV negative and HIV positive DLBCL are similar except for median age, and frequency of elevated LDH levels. Several clinicopathological factors were prognostic for all DLBCL cases including age, gender, stage and bone marrow involvement. In addition, tumour extranodal site was also a prognostic indicator for the HIV negative cohort. The biomarkers identified in the study consisted of four protein clusters including glycolytic enzymes, ribosomal proteins, histones and collagen. These proteins could differentiate between control and tumour tissue, and the DLBCL subtypes in both cohorts. The majority (41/52) of samples in the confirmation cohort were negative for Hsp70 expression. The HIV positive DLBCL cases had a higher percentage of cases expressing Hsp70 than their HIV negative counterparts. The non-GC subtype also frequently overexpressed Hsp70, confirming MALDI IMS data. Expression of Hsp70 correlated with poor outcome in the HIV negative cohort. In conclusion, this study identified potential biomarkers for HIV negative and HIV positive DLBCL from both clinical and molecular sources. These may be used as diagnostic and prognostic markers complementary to current clinical management for DLBCL.en_ZA
dc.identifier.apacitationMagangane, P. S. (2016). <i>Biomarker identification in HIV and non-HIV related lymphomas</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology. Retrieved from http://hdl.handle.net/11427/22817en_ZA
dc.identifier.chicagocitationMagangane, Pumza Samantha. <i>"Biomarker identification in HIV and non-HIV related lymphomas."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2016. http://hdl.handle.net/11427/22817en_ZA
dc.identifier.citationMagangane, P. 2016. Biomarker identification in HIV and non-HIV related lymphomas. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Magangane, Pumza Samantha AB - DLBCL is the most common lymphoma subtype occurring in older populations as well as in younger HIV infected patients. The current treatment options for DLBCL are effective for most patients yet the relapse rate is high. While many biomarkers for DLBCL exist, they are not in clinical use due to low sensitivity and specificity. In addition, these biomarkers have not been studied in the HIV context. Therefore, the identification of new biomarkers for HIV negative and HIV positive DLBCL, may lead to a better understanding of the disease pathology and better therapeutic design. Initially differences in the clinicopathological features between HIV negative and HIV positive DLBCL patients were determined by conducting a retrospective study of patients treated at GSH. Subsequent to this, potential protein biomarkers for DLBCL were determined using MALDI imaging mass spectrometry (IMS) and characterised using LCMS. The expression of one of the biomarkers, heat shock protein (Hsp) 70, was confirmed on a separate cohort of samples using immunohistochemistry. Our results indicate that the clinicopathological features for HIV negative and HIV positive DLBCL are similar except for median age, and frequency of elevated LDH levels. Several clinicopathological factors were prognostic for all DLBCL cases including age, gender, stage and bone marrow involvement. In addition, tumour extranodal site was also a prognostic indicator for the HIV negative cohort. The biomarkers identified in the study consisted of four protein clusters including glycolytic enzymes, ribosomal proteins, histones and collagen. These proteins could differentiate between control and tumour tissue, and the DLBCL subtypes in both cohorts. The majority (41/52) of samples in the confirmation cohort were negative for Hsp70 expression. The HIV positive DLBCL cases had a higher percentage of cases expressing Hsp70 than their HIV negative counterparts. The non-GC subtype also frequently overexpressed Hsp70, confirming MALDI IMS data. Expression of Hsp70 correlated with poor outcome in the HIV negative cohort. In conclusion, this study identified potential biomarkers for HIV negative and HIV positive DLBCL from both clinical and molecular sources. These may be used as diagnostic and prognostic markers complementary to current clinical management for DLBCL. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Biomarker identification in HIV and non-HIV related lymphomas TI - Biomarker identification in HIV and non-HIV related lymphomas UR - http://hdl.handle.net/11427/22817 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22817
dc.identifier.vancouvercitationMagangane PS. Biomarker identification in HIV and non-HIV related lymphomas. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/22817en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Anatomical Pathologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherAnatomical Pathologyen_ZA
dc.titleBiomarker identification in HIV and non-HIV related lymphomasen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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