Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL
| dc.contributor.advisor | Naidoo, Richard | |
| dc.contributor.author | Hlatshwayo, Lerato | |
| dc.date.accessioned | 2021-01-26T12:22:25Z | |
| dc.date.available | 2021-01-26T12:22:25Z | |
| dc.date.issued | 2020 | |
| dc.date.updated | 2021-01-26T12:21:47Z | |
| dc.description.abstract | 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. | |
| dc.identifier.apacitation | Hlatshwayo, L. (2020). <i>Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/32681 | en_ZA |
| dc.identifier.chicagocitation | Hlatshwayo, Lerato. <i>"Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2020. http://hdl.handle.net/11427/32681 | en_ZA |
| dc.identifier.citation | Hlatshwayo, L. 2020. Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL. . ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. http://hdl.handle.net/11427/32681 | en_ZA |
| dc.identifier.ris | TY - Master Thesis AU - Hlatshwayo, Lerato AB - 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. DA - 2020 DB - OpenUCT DP - University of Cape Town KW - Medicine LK - https://open.uct.ac.za PY - 2020 T1 - Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL TI - Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL UR - http://hdl.handle.net/11427/32681 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/32681 | |
| dc.identifier.vancouvercitation | Hlatshwayo L. Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2020 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/32681 | en_ZA |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Clinical Laboratory Sciences | |
| dc.publisher.faculty | Faculty of Health Sciences | |
| dc.subject | Medicine | |
| dc.title | Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL | |
| dc.type | Master Thesis | |
| dc.type.qualificationlevel | Masters | |
| dc.type.qualificationlevel | MSc |