Abstract:
Malignant pleural mesothelioma (MPM) arises in the lining of lungs. MPM
shown non-specific symptoms at early stages. Mostly, the pleura is affected by expo-
sure of asbestos. According to different studies, many factors like genetic mutation or
carbon nanotubes, nano technological products, and ionizing radiation can be cause
of malignant mesothelioma (MM). The difficulty in diagnosing mesothelioma leads
to its worse prognosis. However, when patient diagnosed with mesothelioma, it is
always fatal. The WHO database reported 92,253 deaths in 83 countries from 1994 to
2008 due to malignant mesothelioma. The aim of this study is that find a therapeutic
target for MPM because all bio markers and therapeutic targets have low sensitivity or
low specificity. For this study differential expression analysis was performed on 5 mi-
croarrays and 2 RNA-seq datasets obtained from publicly available databases. For find
the common deferentially expressed genes, we performed comparative analysis of all
data sets. There were 74 common genes between Affymetrix and Agilent. Two genes
were common between microarray and RNA-Seq datasets. Pathway analysis was also
performed to identify effected pathways. We found TOP2A common upregulated
gene in all datasets except Agilent. The most significant pathways were Cell Cycle,
Mitotic, Mitotic G1 phase, G1/S transition, Cell Cycle, Molecules associated with
elastic fibres, G0 and Early G1, Condensation of Prometaphase Chromosomes, G1/S-
Specific Transcription and Elastic fibre formation. We performed blastp of TOP2A
gene. After last step, 4FM9 protein was selected. Then protein was docked with 160
energy minimized ligands. Vinblastine Sulfate ligand showed highest binding affinity
(-11.1) and its ID is CHEMBL378544. Protein-ligand interaction was performed to
identify how ligands interact with selected protein. Vinblastine Sulfate show hydrogen
bonds with protein on Arginine, Glutamine and Lysine amino acid.
