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A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Drug repositioning in head and neck squamous cell carcinoma: An integrated pathway analysis based on connectivity map
Gan-Guan Wei1, Li Gao2, Zheng-Yi Tang1
1Department of Otolaryngology Head and Neck Surgery, NO.303 Hospital of PLA, Nanning, Guangxi Zhuang Autonomous Region, China.
Abstract:
The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC.
Insights
This study identifies potential new therapies for head and neck squamous cell carcinoma (HNSCC) by screening existing drugs. Researchers found two drugs, MG-262 and bepridil, may effectively target PCNA to combat HNSCC.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Head and neck squamous cell carcinoma (HNSCC) poses a significant health burden.
- Novel anti-cancer therapies are urgently needed.
- Drug repositioning offers an efficient strategy for discovering new cancer treatments.
Purpose of the Study:
- To screen candidate drugs for HNSCC treatment using drug repositioning.
- To identify key molecular pathways and targets involved in HNSCC.
- To explore the molecular mechanisms underlying HNSCC.
Main Methods:
- Integrated HNSCC-related pathways (from DEGs) with drug-affected pathways (from CMAP).
- Constructed drug-target and protein-protein interaction (PPI) networks.
- Utilized TCGA, GTEx, HPA, and cBioPortal databases for gene expression and protein data.
- Performed molecular docking analysis to validate drug-target interactions.
Main Results:
- Identified 401 differentially expressed genes (DEGs) in HNSCC.
- Discovered 22 candidate drugs targeting cell cycle and p53 signaling pathways.
- Identified PCNA and CCND1 as critical targets with elevated expression in HNSCC.
- MG-262 and bepridil showed potential to inhibit HNSCC by targeting PCNA.
Conclusions:
- MG-262 and bepridil are promising candidate drugs for HNSCC treatment.
- Targeting PCNA represents a potential therapeutic strategy for HNSCC.
- This study provides a foundation for developing novel HNSCC medications through drug repositioning.
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