Identification of potential drugs for diffuse large b-cell lymphoma based on bioinformatics and Connectivity Map database.

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is the most main subtype in non-Hodgkin lymphoma. After chemotherapy, about 30% of patients with DLBCL develop resistance and relapse. This study was to identify potential therapeutic drugs for DLBCL using the bioinformatics method. The differentially expressed genes (DEGs) between DLBCL and non-cancer samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The R software package (SubpathwayMiner) was used to perform pathway analysis on DEGs affected by drugs found in the Connectivity Map (CMap) database. Protein-protein interaction (PPI) networks of DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes online database and Cytoscape software. In order to identify potential novel drugs for DLBCL, the DLBCL-related pathways and drug-affected pathways were integrated. The results showed that 1927 DEGs were identified from TCGA and GEO. We found 54 significant pathways of DLBCL using KEGG pathway analysis. By integrating pathways, we identified five overlapping pathways and 47 drugs that affected these pathways. The PPI network analysis results showed that the CDK2 is closely associated with three overlapping pathways (cell cycle, p53 signaling pathway, and small cell lung cancer). The further literature verification results showed that etoposide, rinotecan, methotrexate, resveratrol, and irinotecan have been used as classic clinical drugs for DLBCL. Anisomycin, naproxen, gossypol, vorinostat, emetine, mycophenolic acid and daunorubicin also act on DLBCL. It was found through bioinformatics analysis that paclitaxel in the drug-pathway network can be used as a potential novel drug for DLBCL.