Identification of key candidate genes involved in melanoma metastasis

Abstract

Metastasis is the most lethal stage of cancer progression. The present study aimed to investigate the underlying molecular mechanisms of melanoma metastasis using bioinformatics. Using the microarray dataset GSE8401 from the Gene Expression Omnibus database, which included 52 biopsy specimens from patients with melanoma metastasis and 31 biopsy specimens from patients with primary melanoma, differentially expressed genes (DEGs) were identified, subsequent to data preprocessing with the affy package, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed. Mutated genes were analyzed with 80 mutated cases with melanoma from The Cancer Genome Atlas. The overall survival of key candidate DEGs, which were within a filtering of degree >30 criteria in the PPI network and involved three or more KEGG signaling pathways, and genes with a high mutation frequency were delineated. The expression analysis of key candidate DEGs, mutant genes and their associated genes were performed on UALCAN. Of the 1,187 DEGs obtained, 505 were upregulated and 682 were downregulated. ‘Extracellular exosome’ processes, the ‘amoebiasis’ pathway, the ‘ECM-receptor interaction’ pathway and the ‘focal adhesion’ signaling pathway were significantly enriched and identified as important processes or signaling pathways. The overall survival analysis of phosphoinositide-3-kinase regulator subunit 3 ( PIK3R3 ), centromere protein M ( CENPM ), aurora kinase A ( AURKA ), laminin subunit α 1 ( LAMA1 ), proliferating cell nuclear antigen ( PCNA ), adenylate cyclase 1 ( ADCY1 ), BUB1 mitotic checkpoint serine/threonine kinase ( BUB1 ), NDC80 kinetochore complex component ( NDC80 ) and protein kinase C α ( PRKCA ) in DEGs was statistically significant. Mutation gene analysis identified that BRCA1-associated protein 1 ( BAP1 ) had a higher mutation frequency and survival analysis, and its associated genes in the BAP1 -associated PPI network, including ASXL transcriptional regulator 1 ( ASXL1 ), proteasome 26S subunit, non-ATPase 3 ( PSMD3 ), proteasome 26S subunit, non ATPase 11 ( PSMD11 ) and ubiquitin C ( UBC ), were statistically significantly associated with the overall survival of patients with melanoma. The expression levels of PRKCA, BUB1, BAP1 and ASXL1 were significantly different between primary melanoma and metastatic melanoma. Based on the present study, ‘extracellular exosome’ processes, ‘amoebiasis’ pathways, ‘ECM-receptor interaction’ pathways and ‘focal adhesion’ signaling pathways may be important in the formation of metastases from melanoma. Th...

Cancer cell line-specific protein profiles in extracellular vesicles identified by proteomics

“…For the top 20 highly expressed proteins in the EVs isolated from the H3 cell line, LAMA1 and LAMB1, as well as CSPG4, stand out. Here, LAMA1 and LAMB1 have been identified as potential markers for cutaneous melanoma metastasis as these proteins are involved in the modulation of cell adhesion and migration [ 37 , 56 , 57 ]. Also implicated in those latter processes is CSPG4 [ 37 ].…”

Upregulation of CENPM facilitates tumor metastasis via the mTOR/p70S6K signaling pathway in pancreatic cancer

“…Recently, Yu et al defined CENPM as a complement to AFP in the diagnosis of hepatocellular carcinoma ( 8 ); Xiao et al further confirmed that CENPM was highly associated with hepatocellular carcinoma progression and could be a candidate novel biomarker for hepatocellular carcinoma ( 28 ). Investigations of the underlying mechanisms of melanoma highlighted that CENPM may play an important role in the metastases of melanoma ( 9 ). Chen et al suggested that CENPM may contribute to bladder cancer development and cancer recurrence ( 12 ).…”

“…Centromere protein M (CENPM) has been reported as a novel biomarker of hepatocellular carcinoma (8), melanoma (9) and bladder cancer (10). However, the function of CENPM has not been studied in pancreatic cancer.…”

Short-Term Microgravity Influences Cell Adhesion in Human Breast Cancer Cells

“…This result was not significant, and thus it may be speculated that PRKCA is upregulated later, when the cell detachment starts as well as the 3D aggregation of breast cancer cells [40]. In addition, PRKCA is also a key candidate gene in melanoma metastasis [77]. An important step for metastasis is that protein kinase C alpha activates RAF-1 by direct phosphorylation [78].…”