Identification of the interaction network of hub genes for melanoma treated with vemurafenib based on microarray data.

Abstract

AIMS AND BACKGROUND:

The objective of this study was to identify possible biomarkers and to explore the mechanisms of suppression of vemurafenib on melanoma progression.

METHODS:

GSE42872 affymetrix microarray data were downloaded from the Gene Expression Omnibus database for further analysis. Differentially expressed genes (DEGs) between vehicle-treated samples and vemurafenib-treated samples were identified. Gene ontology and pathway enrichment analysis of DEGs were performed, followed by protein-protein interaction (PPI) network construction. Furthermore, the functional modules of the PPI network were screened using BioNet analysis tool. Finally, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for DEGs in the module.

RESULTS:

In total, 794 upregulated transcripts corresponding to 214 genes and 977 downregulated transcripts corresponding to 325 genes were screened. The downregulated DEGs were significantly enriched in pathways such as cell cycle, DNA replication, and p53 signaling pathway. Upregulated DEGs were significantly enriched in phosphatidylinositol signaling system and inositol phosphate metabolism. Significantly enriched functions of downregulated DEGs were mitotic cell cycle, nuclear division, DNA metabolic process, cell cycle, and mitosis. Upregulated DEGs were mainly enriched in single multicellular organism process and multicellular organismal process. Moreover, cell division cycle 6, checkpoint kinase 1 (CHEK1), E2F transcription factor 1 (E2F1), epidermal growth factor receptor (EGFR), and phosphoinositide-3-kinase, regulatory subunit 1-α (PIK3R1) of the module were remarkably enriched in pathways such as cell cycle, apoptosis, focal adhesion, and DNA replication.

CONCLUSIONS:

Cell division cycle 6, CHEK1, E2F1, EGFR, and PIK3R1 of the module and their relative pathways, cell cycle, and focal adhesion might play important roles of suppression of vemurafenib on melanoma progression.

• Authors: Liangliang Quan, Yang Wang, Jiulong Liang, Jie Shi, Yu Zhang, Kai Tao
• Journal: Tumori (Tumori) 2015 Jul-Aug Vol. 101 Issue 4 Pg. 368-74 ISSN: 2038-2529 [Electronic] United States
• PMID: 25983087 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• E2F1 Transcription Factor
• E2F1 protein, human
• Indoles
• Inositol Phosphates
• Phosphatidylinositols
• Sulfonamides
• Tumor Suppressor Protein p53
• Vemurafenib
• Protein Kinases
• PIK3R1 protein, human
• Class Ia Phosphatidylinositol 3-Kinase
• EGFR protein, human
• ErbB Receptors
• CHEK1 protein, human
• Checkpoint Kinase 1

Topics

• Antineoplastic Agents (therapeutic use)
• Apoptosis (genetics)
• Cell Adhesion (genetics)
• Cell Cycle (genetics)
• Checkpoint Kinase 1
• Class Ia Phosphatidylinositol 3-Kinase
• DNA Replication (genetics)
• Down-Regulation
• E2F1 Transcription Factor (metabolism)
• ErbB Receptors (metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Indoles (therapeutic use)
• Inositol Phosphates (metabolism)
• Melanoma (drug therapy, genetics)
• Microarray Analysis
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphatidylinositols (metabolism)
• Protein Kinases (metabolism)
• Signal Transduction (genetics)
• Skin Neoplasms (drug therapy, genetics)
• Sulfonamides (therapeutic use)
• Tumor Suppressor Protein p53 (metabolism)
• Up-Regulation
• Vemurafenib