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Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL
Introduction: Diffused large B-cell lymphomas (DLBCL) is the most common aggressive nonHodgkin lymphoma (NHL) worldwide, constituting up to 40% of all cases globally. The incidence of HIV-associated lymphoma has decreased since the introduction of combination antiretroviral therapy (cART) in the mid...
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| Format: | Thesis |
| Language: | English |
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Department of Clinical Laboratory Sciences
2021
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| _version_ | 1867611297359593472 |
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| access_status_str | Open Access |
| author | Hlatshwayo, Lerato |
| author2 | Naidoo, Richard |
| author_browse | Hlatshwayo, Lerato Naidoo, Richard |
| author_facet | Naidoo, Richard Hlatshwayo, Lerato |
| author_sort | Hlatshwayo, Lerato |
| collection | Thesis |
| description | Introduction: Diffused large B-cell lymphomas (DLBCL) is the most common aggressive nonHodgkin lymphoma (NHL) worldwide, constituting up to 40% of all cases globally. The incidence of HIV-associated lymphoma has decreased since the introduction of combination antiretroviral therapy (cART) in the mid-1990s. However, NHL, especially DLBCL remains the most common cause of morbidity and mortality among people living with HIV/AIDS, especially in sub-Saharan Africa where 70% of the global HIV/AIDS population reside. Gene expression profiles (GEP) identified based on the cell of origin (COO) two distinct DLBCL subtypes; germinal-centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. These subtypes differ in their genetic abnormalities and response to treatment regimens. Aim: We aimed to investigate in detail, protein distribution profile from FFPE tissue in HIV and non-HIV related DLBCL subtypes. Methods: FFPE DLBCL lymph node tissue samples from HIV and non-HIV related DLBCL were subjected to MALDI-imaging, in order to get the spatial distribution of proteins in DLBCL tissue. Proteins were extracted from tissue samples and subjected to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to identify proteins present in FFPE DLBCL tissue. The protein profiles from the above-mentioned samples were compared and characterized by cancer pathways. Results: This study had 12 DLBCL cases and 2 human tonsil controls diagnosed from 2009- 2011. These cases were retrieved using the NHLS database. The overall age of DLBCL patients by the time they were diagnosed ranged from 18 to 73 years, with a median age of 48 years. MALDI-IMS peak detection function identified 1466 different m/z values from both the HIV negative and HIV positive DLBCL cases. There were only 50 exclusive m/z values that distinguished the DLBCL subtypes, Using LC-MS/MS we identified a total of 88 proteins, by comparing these proteins, we observed 6 differentially expressed among the DLBCL subtypes and controls Fructose-bisphosphate aldolase C was the only significantly differentially expressed proteins between HIV negative ABC DLBCL and HIV positive ABC DLBCL subtype (p value=1,47738). 10 Conclusion: Using proteomic techniques, we identified and visualized differentially expressed protein in DLBCL subtypes and controls. The majority of these proteins belonged to glycolysis, ATP synthesis, and cellular movement. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/32681 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Department of Clinical Laboratory Sciences |
| publisherStr | Department of Clinical Laboratory Sciences |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/32681 Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL Hlatshwayo, Lerato Naidoo, Richard Medicine Introduction: Diffused large B-cell lymphomas (DLBCL) is the most common aggressive nonHodgkin lymphoma (NHL) worldwide, constituting up to 40% of all cases globally. The incidence of HIV-associated lymphoma has decreased since the introduction of combination antiretroviral therapy (cART) in the mid-1990s. However, NHL, especially DLBCL remains the most common cause of morbidity and mortality among people living with HIV/AIDS, especially in sub-Saharan Africa where 70% of the global HIV/AIDS population reside. Gene expression profiles (GEP) identified based on the cell of origin (COO) two distinct DLBCL subtypes; germinal-centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. These subtypes differ in their genetic abnormalities and response to treatment regimens. Aim: We aimed to investigate in detail, protein distribution profile from FFPE tissue in HIV and non-HIV related DLBCL subtypes. Methods: FFPE DLBCL lymph node tissue samples from HIV and non-HIV related DLBCL were subjected to MALDI-imaging, in order to get the spatial distribution of proteins in DLBCL tissue. Proteins were extracted from tissue samples and subjected to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to identify proteins present in FFPE DLBCL tissue. The protein profiles from the above-mentioned samples were compared and characterized by cancer pathways. Results: This study had 12 DLBCL cases and 2 human tonsil controls diagnosed from 2009- 2011. These cases were retrieved using the NHLS database. The overall age of DLBCL patients by the time they were diagnosed ranged from 18 to 73 years, with a median age of 48 years. MALDI-IMS peak detection function identified 1466 different m/z values from both the HIV negative and HIV positive DLBCL cases. There were only 50 exclusive m/z values that distinguished the DLBCL subtypes, Using LC-MS/MS we identified a total of 88 proteins, by comparing these proteins, we observed 6 differentially expressed among the DLBCL subtypes and controls Fructose-bisphosphate aldolase C was the only significantly differentially expressed proteins between HIV negative ABC DLBCL and HIV positive ABC DLBCL subtype (p value=1,47738). 10 Conclusion: Using proteomic techniques, we identified and visualized differentially expressed protein in DLBCL subtypes and controls. The majority of these proteins belonged to glycolysis, ATP synthesis, and cellular movement. 2021-01-26T12:22:25Z 2021-01-26T12:22:25Z 2020 2021-01-26T12:21:47Z Master Thesis Masters MSc http://hdl.handle.net/11427/32681 eng application/pdf Department of Clinical Laboratory Sciences Faculty of Health Sciences |
| spellingShingle | Medicine Hlatshwayo, Lerato Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL |
| thesis_degree_str | Master's |
| title | Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL |
| title_full | Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL |
| title_fullStr | Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL |
| title_full_unstemmed | Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL |
| title_short | Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL |
| title_sort | investigation of protein biomarkers in hiv positive and hiv negative associated dlbcl |
| topic | Medicine |
| url | http://hdl.handle.net/11427/32681 |
| work_keys_str_mv | AT hlatshwayolerato investigationofproteinbiomarkersinhivpositiveandhivnegativeassociateddlbcl |