Background:Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers, causing about 72% of deaths in skin carcinoma. Although extensive study has explored the mechanism of recurrence and metastasis, the tumorigenesis of cutaneous melanoma remains unclear. Exploring the tumorigenesis mechanism may help identify prognostic biomarkers that could serve to guide cancer therapy. Methods:Integrative bioinformatics analyses, including GEO database, TCGA database, DAVID, STRING, Metascape, GEPIA, cBioPortal, TRRUST, TIMER, TISIDB and DGIdb, were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of SKCM. Furthermore, immunohistochemistry (IHC) staining was performed to validate differential expression levels of hub genes between SKCM tissue and normal tissues from the First Affiliated Hospital of Soochow University cohort. Results: A total of 308 differentially expressed genes (DEGs) and 12 hub genes were found significantly differentially expressed between SKCM and normal skin tissues. Functional annotation indicated that inflammatory response, immune response was closely associated with SKCM tumorigenesis. KEGG pathways in hub genes include IL-10 signaling and chemokine receptors bind chemokine signaling. Five chemokines members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) were associated with better overall survival and pathological stages. IHC results suggested that significantly elevated CXCL9, CXCL10, CXCL13, CCL4 and CCL5 proteins expressed in the SKCM than in the normal tissues. Moreover, our findings suggested that IRF7, RELA, NFKB1, IRF3 and IRF1 are key transcription factors for CCL4, CCL5, CXCL10. In addition, the expressions of CXCL9, CXCL10, CXCL13, CCL4 and CCL5 were positively correlated with infiltration of six immune cells (B-cell, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells) and 28 types of TILs. Among them, high levels of B cells, CD8+T cells, neutrophils and dendritic cells were significantly related to longer SKCM survival time. Conclusion: In summary, this study mainly identified five chemokine members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) associated with SKCM tumorigenesis, progression, prognosis and immune infiltrations, which might help us evaluate several immune-related targets for cutaneous melanoma therapy.
Background: Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with non-melanoma skin cancers (NMSC). However, unclear pathogenesis of cSCC limits the application of molecular targeted therapy. Results: To identify the hub genes in the pathogenesis and progression of cSCC, we downloaded the microarray data sets GSE2503, GSE45164 and GSE66359 from the Gene Expression Omnibus (GEO) database, and identified differentially expressed genes (DEGs) between tumor and non-tumor tissues. Functional enrichment analysis was performed using DAVID. The STRING online website was used to construct a protein-protein interaction network (PPI), and then Cytoscape performed module analysis and degree calculation. 146 DEGs were identified with significant differences, including 113 up-regulated genes and 33 down-regulated genes. The enriched functions and pathways of the DEGs include microtubule-based movement, ATP binding, cell cycle, p53 signaling pathway, oocyte meiosis and PLK1 signaling events. Nine hub genes were identified, namely CDK1, AURKA, RRM2, CENPE, CCNB1, KIAA0101, ZWINT, TOP2A, ASPM. The differential expression of these genes has been verified in other data sets. In addition, the ROC curve also confirmed their ability to predict disease. Conclusion: By integrated bioinformatic analysis, the DEGs and hub genes identified in this study elucidated the molecular mechanism of the pathogenesis and progression of cSCC, and are expected to become future biomarkers or therapeutic targets.
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