Malaria and Burkitt’s Lymphoma: An In Silico Analysis of Gene Expression Links between Malaria and Burkitt’s Lymphoma and Potential Anticancer Activity of Artemisinin Derivatives

Abstract

BackgroundBurkitts lymphoma (BL) is an aggressive form of B-cell non-Hodgkin lymphoma. Endemic subtype of the disease showed a remarkable statistical and epidemiological association with malaria infection. Despite the numerous studies performed to explain this association; molecular mechanisms underlie such coincidence still remain unclear. Dissecting molecular mechanisms which link Malaria infection and Burkitts lymphoma can provide insights about reported anticancer action of certain antimalarial drugs, namely artemisinin derivatives.\n\nMethodsHere we applied an integrative approach to investigate for potential links between malaria infection and endemic Burkitts lymphoma regarding their gene expression, and further explore common molecular mechanisms through which artemisinin compounds might act in endemic Burkitts lymphoma. Using gene expression data of malaria (Plasmodium falciparum infected erythroblasts) and endemic Burkitts lymphoma from Gene Expression Omnibus database, expression patterns in the two conditions were examined through clustering analysis using Self Organizing Maps, and then by significance testing of differentially expressed genes in each condition followed by Functional annotation using Gene Ontology clustering and Pathways analysis.\n\nResultsClustering analysis identified a significant overlap between the expression patterns in endemic Burkitts lymphoma and Plasmodium falciparum infected cells. Four out of the 12 identified clusters contained genes with similar expression patterns in both conditions. Differential expression analysis identified 1689 genes as significantly differentially expressed in endemic Burkitts lymphoma and 405 in malaria. Those genes were found to be related to important Gene Ontology terms and pathways. Interestingly 65% of the identified pathways in Malaria were overlapped with those identified in endemic Burkitts lymphoma. Several of these pathways reported to be related to actions of artemisinin derivatives.\n\nConclusionOur In-silico analysis showed a significant molecular convergence between endemic Burkitts lymphoma and malaria. A number of 43pathways which demonstrated enrichment in tumour were shared with Plasmodium falciparum infected erythrocytes. Such pathways represent potential targets for antimalarial drugs to exert therapeutic effects in such malignancy.