Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL

Hlatshwayo, Lerato

Investigation of protein biomarkers in HIV positive and HIV negative associated DLBCL

Master Thesis

2020

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.

Keywords

Medicine

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