Abstract
Simple SummaryEcotropic viral integration site 2B (EVI2B) is a protein-coding gene known as a lymphocyte-specific marker in peripheral blood. However, the prognostic value of EVI2B expression in metastatic melanoma tissue and its detailed profile of tumor-infiltrating lymphocytes are still unclear. In publicly available datasets, we found that increased EVI2B was significantly associated with longer prognoses such as overall survival and disease-specific survival. The EVI2B-high melanoma tissue had a favorable distribution/clustering pattern of infiltrating lymphocytes with increased CD8+ T cells over regulatory T cells. Moreover, EVI2B expression correlated with multiple immunomodulatory genes including IFN-γ signature genes. In conclusion, EVI2B is a prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.Background: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. Methods: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE65904 and GSE19234). Results: The univariate and multivariate analyses showed that higher gene expression of EVI2B was significantly associated with longer prognoses. The EVI2B-high melanoma tissue had favorable histological parameters such as a brisk global distribution pattern and clustering structure of TILs (i.e., Banfield and Raftery index) with enriched CD8+ T cells over regulatory T cells and increased cytotoxicity scores. In addition, EVI2B expression positively correlated with IFN-γ signature genes (CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, and STAT1) and other various immunomodulatory genes. Conclusion: EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.
Highlights
Cutaneous melanoma is a malignant tumor originating from melanocytes [1]
We investigated the prognostic value of ecotropic viral integration site 2B (EVI2B) gene expressions using the metastatic melanoma datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets
We investigated the survival data from TCGA in metastatic melanoma patients with EVI2B gene expression
Summary
Cutaneous melanoma is a malignant tumor originating from melanocytes [1]. the incidence rate of melanoma is lower than other skin cancers, it is responsible for most metastatic skin cancer–related deaths [2,3]. Melanoma is an immunogenic tumor with multiple types of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) [4]. The TME profile is closely associated with the therapeutic success of immune checkpoint blockade [6]. Analyzing the TME of melanoma may help better understand the immunological interactions between the tumor and the host cells and how such interactions influence the clinical outcomes. No study has previously investigated EVI2B as a potential biomarker in metastatic melanoma. We investigated the prognostic value of EVI2B gene expressions using the metastatic melanoma datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Our evaluation showed that EVI2B was associated with gene signatures that were associated with a better response to immune checkpoint blockades such as anti-PD1 or anti-CTLA4 antibody therapies [18,19]
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