Screening and identification of key genes and pathways in metastatic uveal melanoma based on gene expression using bioinformatic analysis

Abstract

The current study aimed to elucidate the molecular mechanisms and identify the potential key genes and pathways for metastatic uveal melanoma (UM) using bioinformatics analysis. Gene expression microarray data from GSE39717 included 39 primary UM tissue samples and 2 metastatic UM tissue samples. Differentially expressed genes (DEGs) were generated using Gene Expression Omnibus 2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. The web-based STRING tool was adopted to construct a protein--protein interaction (PPI) network. The MCODE tool in Cytoscape was used to generate significant modules of the PPI network. A total of 213 DEGs were identified. GO and KEGG analyses revealed that the upregulated genes were mainly enriched in extracellular matrix organization and blood coagulation cascades, while the downregulated DEGs were mainly related to protein binding, negative regulation of ERK cascade, nucleus and chromatin modification, and lung and renal cell carcinoma. The most significant module was extracted from the PPI network. GO and KEGG enrichment analyses of the module revealed that the genes were mainly enriched in the extracellular region and space organization, blood coagulation process, and PI3K-Akt signaling pathway. Hub genes, including FN1, APOB, F2, SERPINC1, SERPINA1, APOA1, FGG, PROC, ITIH2, VCAN, TFPI, CXCL8, CDH2 , and HP, were identified from DEGs. Survival analysis and hierarchical clustering results revealed that most of the hub genes were associated with prognosis and clinical progression. Results of this bioinformatics analysis may provide predictive biomarkers and potential candidate therapeutic targets for individuals with metastatic UM.

Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction

“…In combination with KMT2A overexpression, AFF1 is associated with poor prognosis in acute lymphoblastic leukemia 83 . ITIH2 was recently identified as a core gene for colorectal cancer liver metastasis, with overexpression associated with poor survival, 84 and as a hub gene in metastatic uveal melanoma, 85 whereas in multiple other primary solid tumors, downregulation of ITIH2 is identified 86 . Elevations of serum ITIH2 are associated with metabolic dysfunction in obese dogs compared to those without metabolic dysfunction 87 .…”

A prognostic index model for assessing the prognosis of ccRCC patients by using the mRNA expression profiles of AIF1L, SERPINC1 and CES1

“…Previous studies have reported that SERPINC1 expression is upregulated in nasopharyngeal carcinoma tissue [37], bladder cancer tissue [37], endometrial and exosome cancer tissue [38] compared to adjacent normal tissues. SERPINC1 expression was also strongly associated with the development occurrence and progression of certain tumor types [39][40][41] and has been identified as an immune-related gene. SERPINC1 expression is prognostic for the survival of lung adenocarcinoma41, uveal melanoma [40] and hepatocellular carcinoma [41] patients.…”

Aging and Obesity Prime the Methylome and Transcriptome of Adipose Stem Cells for Disease and Dysfunction

“…82 In combination with KMT2A overexpression, AFF1 is associated with poor prognosis in acute lymphoblastic leukemia. 83 ITIH2 was recently identified as a core gene for colorectal cancer liver metastasis, with overexpression associated with poor survival, 84 and as a hub gene in metastatic uveal melanoma, 85 whereas in multiple other primary solid tumors, downregulation of ITIH2 is identified. 86 Elevations of serum ITIH2 are associated with metabolic dysfunction in obese dogs compared to those without metabolic dysfunction.…”