Identification of biomarkers and pathways associated with immune infiltration and prognosis in melanoma patients
Abstract Background Skin cutaneous melanoma (SKCM) is one of the most malignancy 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 melanoma remains unclear. Exploring the tumorigenesis mechanism may help to identify prognostic biomarkers that could serve to guide cancer therapy . Methods We identified differentially expressed genes (DEGs) between patients with primary melanoma and normal skin in three data sets including GSE46517, GSE15605, GSE114445. Functional annotation including KEGG pathway and gene ontology (GO) enrichment analysis was performed by DAVID. Subsequently, protein ‐ protein interaction network of DEGs was developed and the most significant module was constructed as hub genes for further study. ClueGO was used to investigate significant pathways in hub genes. The Kaplan–Meier method was performed to assess prognostic genes. ROC curves were used to describe diagnosis value of hub genes. Then, genes expression and clinical characteristics were validated by TCGA profiles. In addition, we explored the correlation between prognostic genes and immune cell infiltration. Results A total of 308 DEGs and 12 hub genes were identified. GO enrichment results demonstrated a correlation between DEGs and the immune response, inflammatory response and transcriptional control. Hallmark pathways of hub genes including interleukin-10 signaling, chemokine receptors bind chemokine signaling , peptide ligand-binding receptors. Survival analysis and ROC curves suggested that CCL4, CCL5, NMU, CXCL9, CXCL10, CXCL13 were independent prognostic factors (except GAL). Furthermore, prognostic genes were highly expressed in tumor tissue and related to pathological stages and Breslow depth. In addition, the expressions of CCL4, CCL5, CXCL9, CXCL10, CXCL13 were positively correlated with six immune cell infiltration (B-cell, CD8+ T cells, CD4+ T cells, macrophages, Neutrophils, Dendritic cells) and 28 types of TILs such as activated CD8 T cells, regulatory T cells, natural killer T cells while NMU and GAL were negatively correlated with it. Conclusion In summary, this study identified significant hub genes and pathways closely associated with immune infiltrations and prognosis in SKCM patients, which might help us evaluate underlying carcinogenesis progress from skin to melanoma.