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PURPOSE: To identify the potential differential genes between primary and metastatic melanoma, screen out immune-related genes in core genes and analyze their immune correlation, thus searching for the early diagnostic biomarkers of cutaneous malignant melanoma (CMM) and the targets of curbing metastasis. MATERIALS AND METHODS: We analyzed two microarray datasets (GSE8401 and GSE46517) derived from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between primary and metastatic melanoma were screened out using the GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify the functions and pathways of DEGs. We analyzed protein-protein interaction of these DEGs based on the Search Tool for the Retrieval of Interacting Genes database and showed by Cytoscape software. In addition, the online Gene Expression Profiling Interactive Analysis tool (GEPIA) was used to analyze the prognostic value of hub genes expressed in metastatic melanoma patients. Immune-related genes in hub genes were screened and further analyzed. RESULTS: A total of 178 upregulated DEGs and 4 downregulated DEGs were identified. 23 terms and 4 pathways were confirmed related to metastatic melanoma. Ten hub genes with a high degree of connectivity were found. Overexpression of three hub genes (DSG1, FLG, PKP1) (P<0.01) was associated with metastasis and poor prognosis of CMM. Among them, the patients with overexpression of PKP1 suffered shorter survival. In addition, 2 immune-related genes (EGFR and CDH1) in hub genes were screened out and both of them were related to anti-tumor immunity, although their expression level did not affect the overall survival of CMM patients significantly. CONCLUSION: Our study suggests that DSG1, FLG and PKP1 were overexpressed in metastatic melanoma compared with primary melanoma, and overexpression of these three genes was an unfavorable prognostic factor ifor CMM patients, which may indicate that they are associated with promoting metastasis of malignant melanoma. EGFR and CDH1 play a crucial role in anti-tumor immunity for CMM. Further research is needed to explore the value of these genes in the inhibition of metastasis and treatment of CMM.
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PURPOSE: To construct a prognostic model of breast cancer using ferroptosis-related lncRNAs and explore novel therapeutic targets. MATERIALS AND METHODS: A prognostic characteristic model based on differential expression of ferroptosis-related lncRNAs in breast cancer was established based on TCGA data. RESULTS: Eleven ferroptosis-related lncRNAs associated with breast cancer prognosis were identified. Kaplan-Meier analysis suggested that high-risk lncRNA signatures correspond to a poor prognosis. The AUC of the signature lncRNAs was 0.682, demonstrating that it is accurate in predicting BC prognosis. GSEA showed that ferroptosis-related lncRNAs in high-risk individuals are mainly enriched in cell cycle, cell adhesion and tumor pathways. Immunity and gene expression analysis revealed that APC co-inhibition, check-point, HLA, inflammation-promoting and T cell co-stimulation among others were significantly different between the high-and low-risk group. Three immune checkpoints were highly expressed in the high-risk group. CONCLUSION: Ferroptosis-related lncRNAs can be used as a prognostic feature to construct a prognostic model of breast cancer, based on which early detection markers, therapeutic targets and anti-tumor immune microenvironment can be studied, and clinical treatment can also be instructive.
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Dysregulation of microRNA (miRNA) expression in multiple cancers and their vital roles in malignant cancer progression are well investigated. The purpose of this study was to explore the biological roles of miR-876-3p in pancreatic cancer. We used genome-wide gene expression analysis in clinical pancreatic adenocarcinoma samples to identify miR-876-3p down-regulated in pancreatic cancer. We then collected 22 pairs of pancreatic cancer and the corresponding non-cancerous tissues to determine miR-876-3p level, and confirmed that miR-876-3p was significantly down-regulated in pancreatic cancer. Furthermore, functional analysis suggested that overexpression of miR-876-3p suppressed cell growth and aggressively increased cells apoptosis in BXPC-3 and PANC-1 cells, whereas down-regulation led to the opposite results. We identified Jagged2 (JAG2) as a direct target of miR-876-3p, and an inverse correlation between miR-876-3p and JAG2 was observed in pancreatic adenocarcinoma. Moreover, miR-876-3p and a JAG2 siRNA were co-transfected into both PANC-1 and BXPC-3 cells to explore the mechanism of miR-876-3p and JAG2 on pancreatic adenocarcinoma tumorigenesis. Down-regulation of JAG2 inhibited the overexpression effects of miR-876-3p, and up-regulation of JAG2 reversed the effects of overexpressed miR-876-3p. Cumulatively, these results revealed a significant role of the miR-876-3p/JAG2 axis in suppressing pancreatic adenocarcinoma cell growth and aggressiveness.
