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

AbstractBackgroundBurkitt’s 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 Burkitt’s lymphoma can provide insights about reported anticancer action of certain antimalarial drugs, namely artemisinin derivatives.MethodsHere we applied an integrative approach to investigate for potential links between malaria infection and endemic Burkitt’s lymphoma regarding their gene expression, and further explore common molecular mechanisms through which artemisinin compounds might act in endemic Burkitt’s lymphoma. Using gene expression data of malaria (Plasmodium falciparum infected erythroblasts) and endemic Burkitt’s 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.ResultsClustering analysis identified a significant overlap between the expression patterns in endemic Burkitt’s 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 Burkitt’s 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 Burkitt’s lymphoma. Several of these pathways reported to be related to actions of artemisinin derivatives.ConclusionOur In-silico analysis showed a significant molecular convergence between endemic Burkitt’s 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.