Title:Identification of Novel Key Targets and Candidate Drugs in Oral Squamous Cell Carcinoma
VOLUME: 15 ISSUE: 4
Author(s):Juan Liu, Xinjie Lian, Feng Liu, Xueling Yan, Chunyan Cheng, Lijia Cheng, Xiaolin Sun* and Zheng Shi*
Affiliation:School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015, School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015, School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015, School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015, School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015, School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015, Department of Radiotherapy, the Central Hospital of Xuzhou, Xuzhou 221000, School of Medicine & Sichuan Industrial Institute of Antibiotics & Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu 610015
Keywords:Oral squamous cell carcinoma, novel target, GRB2, IGF1, systems biology, drug discovery.
Abstract:
Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant
epithelial neoplasm. It is located within the top 10 ranking incidence of cancers with a poor
prognosis and low survival rates. New breakthroughs of therapeutic strategies are therefore needed
to improve the survival rate of OSCC harboring patients.
Objective: Since targeted therapy is considered as the most promising therapeutic strategies in
cancer, it is of great significance to identify novel targets and drugs for the treatment of OSCC.
Methods: A series of bioinformatics approaches were launched to identify the hub proteins and
their potential agents. Microarray analysis and several online functional activity network analysis
were firstly utilized to recognize drug targets in OSCC. Subsequently, molecular docking was used
to screen their potential drugs from the specs chemistry database. At the same time, the assessment
of ligand-based virtual screening model was also evaluated.
Results: In this study, two microarray data (GSE31056, GSE23558) were firstly selected and
analyzed to get consensus candidate genes including 681 candidate genes. Additionally, we
selected 33 candidate genes based on whether they belong to the kinases and transcription factors
and further clustered candidate hub targets based on functions and signaling pathways with
significant enrichment analysis by using DAVID and STRING online databases. Then, core PPI
network was then identified and we manually selected GRB2 and IGF1 as the key drug targets
according to the network analysis and previous references. Lastly, virtual screening was performed
to identify potential small molecules which could target these two targets, and such small
molecules can serve as the promising candidate agents for future drug development.
Conclusion: In summary, our study might provide novel insights for understanding of the
underlying molecular events of OSCC, and our discovered candidate targets and candidate agents
could be used as the promising therapeutic strategies for the treatment of OSCC.
