Identification of immune-related biomarkers associated with tumorigenesis and prognosis in cutaneous melanoma patients

Abstract

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.

Identification of Immune-Related Prognostic Biomarkers Associated with HPV-Positive Head and Neck Squamous Cell Carcinoma

“…On this basis, we found that the immune cell components of patients in these two groups were also different, mainly in naïve B cells, memory B cells, plasma cells, CD8 + T cells, naive CD4 + T cells, resting CD4 + memory T cells, activated CD4 + memory T cells, and regulatory T cells, in line with previous findings [ 28 ]. For example, CD8 + T cells play an important role in the tumor microenvironment, which inhibits the proliferation and metastasis of tumor cells [ 29 ]. Our results indicate that CD8 + T cells were highly expressed in low immune risk groups.…”

The Research on the Treatment of Metastatic Skin Cutaneous Melanoma by Huanglian Jiedu Decoction Based on the Analysis of Immune Infiltration Analysis

“…It was found that CXCL12 and CCL27 played an important role in CM metastasis, and were mainly involved in SKMC metastasis through the CXCR4-CXCR7-CXCL12 axis and CCL27-CCR10 axis [ 39 , 40 ]. CXCL9 and CXCL13 have been confirmed to be overexpressed in both primary SKCM and metastatic CM [ 41 , 42 ]. As ligands of CCR7, CCL19 and CCL21 play an important role in the migration of immune cells (T cells and dendritic cells), and deviation in the regulation of the CCR7-CCL19/CCL21 axis may lead to and cause the occurrence and metastasis of tumors [ 43 ].…”

Identification of a five-gene prognostic signature related to B cells infiltration in pancreatic adenocarcinoma

“…Then gene set variation analysis (GSVA) package is applied to calculate the degree of immune cell in ltration based on gene expression pro les [19]. These ways have been employed to estimate the relative abundance of immune cells from various cancers such as hepatocellular carcinoma [20] and cutaneous melanoma [21].…”