Title:Identification of Drug Targets and Agents Associated with Hepatocellular
Carcinoma through Integrated Bioinformatics Analysis
Volume: 23
Issue: 7
Author(s): Md. Alim Hossen, Md. Selim Reza, Md. Harun-Or-Roshid, Md. Ariful Islam, Mst. Ayesha Siddika and Md. Nurul Haque Mollah*
Affiliation:
- Bioinformatics Laboratory, Department of Statistics, University of Rajshahi, Rajshahi, 6205, Bangladesh
Keywords:
Hepatocellular carcinoma, differentially expressed genes (DEGs), hub-degs, drug targets, drug agents, integrated bioinformatics approaches.
Abstract:
Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related
death globally. The mechanisms underlying the development of HCC are mostly unknown till now.
Objective: The main goal of this study was to identify potential drug target proteins and agents for the
treatment of HCC.
Methods: The publicly available three independent mRNA expression profile datasets were downloaded
from the NCBI-GEO database to explore common differentially expressed genes (cDEGs) between
HCC and control samples using the Statistical LIMMA approach. Hub-cDEGs as drug targets highlighting
their functions, pathways, and regulators were identified by using integrated bioinformatics
tools and databases. Finally, Hub-cDEGs-guided top-ranked drug agents were identified by molecular
docking study for HCC.
Results: We identified 160 common DEGs (cDEGs) from three independent mRNA expression datasets
in which ten cDEGs (CDKN3, TK1, NCAPG, CDCA5, RACGAP1, AURKA, PRC1, UBE2T,
MELK, and ASPM) were selected as Hub-cDEGs. The GO functional and KEGG pathway enrichment
analysis of Hub-cDEGs revealed some crucial cancer-stimulating biological processes, molecular functions,
cellular components, and signaling pathways. The interaction network analysis identified three
TF proteins and five miRNAs as the key transcriptional and post-transcriptional regulators of HubcDEGs.
Then, we detected the proposed Hub-cDEGs guided top-ranked three anti-HCC drug molecules
(Dactinomycin, Vincristine, Sirolimus) that were also highly supported by the already published
top-ranked HCC-causing Hub-DEGs mediated receptors.
Conclusion: The findings of this study would be useful resources for diagnosis, prognosis, and therapies
of HCC.