Identification of genes associated with melanoma metastasis

Abstract

The aims of the study were to identify the differentially expressed genes (DEGs) between primary melanomas and metastasis melanomas (MMs), and to investigate the mechanisms of MMs. The microarray data GSE8401 including 31 primary melanomas and 52 MMs were downloaded from Gene Expression Omnibus. DEGs were identified using the Linear Models for Microarray Data package. The functional and pathway enrichment analyses were performed for DEGs. Identification of transcription factors, tumor-associated genes (TAGs), and tumor suppressor genes (TSGs) were performed with the TRANSFAC, TAG, and TSGene databases, respectively. A protein–protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes. The modules construction and analysis was performed using Molecular Complex Detection and Gene Cluster with Literature Profiles, respectively. In total, 1004 upregulated and 1008 downregulated DEGs were identified. The upregulated DEGs, such as CDK1, BRCA1, MAD2L1, and PCNA, were significantly enriched in cell cycles, DNA replication, and mismatch repair. The downregulated DEGs, such as COLIAL, COL4A5, COL18A1, and LAMC2, were enriched in cell adhesion and extracellular matrix-receptor interaction. BRCA1 was identified as a transcription factor and TSG, and COL18A1 and LAMC2 were identified as a TSG and TAG, respectively. The upregulated DEGs had higher degrees in the protein–protein interaction network and module, such as PCNA, CDK1, and MAD2L1, and the heat map showed they were clustered in the functions of cell cycle and division. These results may demonstrate the potential roles of DEGs such as CDK1, BRCA1, COL18A1, and LAMC2 in the mechanism of MM.

Keywords

• Adhesion
• Cell cycle
• COL1A1
• Metastasis melanomas
• PCNA