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Updated: Aug 12, 2025
Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Identification of hub genes involved in cisplatin resistance in head and neck cancer
Raushan Kumar Chaudhary1, Pukar Khanal2, Uday Venkat Mateti3
1Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Deralakatte, Mangaluru, Karnataka, 575018, India.
Background:
Cisplatin resistance is one of the major contributors to the poor survival rate among head and neck cancer (HNC) patients. Focusing on the protein-protein interaction rather than a single protein could provide a better understanding of drug resistance. Thus, this study aimed to identify hub genes in a complex network of cisplatin resistance associated genes in HNC chemotherapy via a series of bioinformatic tools.
Methods:
The genes involved in cisplatin resistance were retrieved from the NCBI gene database using "head and neck cancer" and "cisplatin resistance" as key words. The human genes retrieved were analyzed for their interactions and enriched using the STRING database. The interaction between KEGG pathways and genes was visualized in Cytoscape 3.7.2. Further, the hub gene was identified using the Cytohubba plugin of Cytoscape and validated using UALCAN and Human Protein Atlas database. Validated genes were investigated for the drug-gene interaction using the DGIbd database.
Results:
Out of 137 genes obtained using key words, 133 were associated with cisplatin resistance in the human species. A total of 150 KEGG pathways, 82 cellular components, 123 molecular functions, and 1752 biological processes were modulated on enrichment analysis. Out of 37 hub genes, CCND1, AXL, CDKN2A, TERT, and EXH2 genes were found to have significant (p < 0.05) mRNA expression and effect on overall survival whereas protein expression was found to be positive for all the significant genes except TERT. Thus, they can be targeted with palbociclib, methotrexate, bortezomib and fluorouracil, sorafenib, dasatinib, carboplatin, paclitaxel, gemcitabine, imatinib, doxorubicin, and vorinostat.
Conclusion:
As the pathogenesis of head and neck cancer is complex, targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance which might uplift overall survival among HNC patients.
Insights
Identifying key genes in head and neck cancer (HNC) cisplatin resistance is crucial for improving patient survival. This study pinpointed significant hub genes, offering potential therapeutic targets to overcome drug resistance in HNC chemotherapy.
Area of Science:
- Oncology
- Bioinformatics
- Genomics
Background:
- Cisplatin resistance significantly reduces survival rates in head and neck cancer (HNC) patients.
- Understanding protein-protein interactions offers deeper insights into drug resistance mechanisms compared to single-protein studies.
Purpose of the Study:
- To identify critical hub genes within the complex network of genes associated with cisplatin resistance in HNC.
- To explore potential therapeutic targets for overcoming chemotherapy resistance in head and neck cancers.
Main Methods:
- Genes related to cisplatin resistance in HNC were retrieved from the NCBI gene database.
- Protein-protein interaction networks were constructed and analyzed using STRING and Cytoscape.
- Hub genes were identified using the Cytohubba plugin and validated via UALCAN and Human Protein Atlas databases.
Main Results:
- Analysis identified 133 genes associated with cisplatin resistance, with 37 identified as hub genes.
- CCND1, AXL, CDKN2A, TERT, and EXH2 showed significant mRNA expression and impact on overall survival.
- These validated hub genes are potential targets for various existing chemotherapeutic agents.
Conclusions:
- Targeting identified hub genes and associated pathways represents a promising strategy for managing cisplatin resistance in HNC.
- This approach could lead to significant advancements in drug discovery and improve overall survival for HNC patients.
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