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EVI2B Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration.

ABSTRACT: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. 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). 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. EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.

SUBMITTER: Yonekura S

PROVIDER: S-EPMC8391972 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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<i>EVI2B</i> Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration.

Yonekura Satoru S Ueda Kosuke K

Cancers 20210815 16

<h4>Background</h4>To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma.<h4>Methods</h4>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).<h4>Results</h4>The univariate and multivariate analyses showed that higher ge ...[more]

PMID: 34439264

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Project description:Background: Sirtuin 7 (SIRT7), a protein-coding gene whose abnormal expression and function are associated with carcinogenesis. However, the prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear. Methods: The expression and survival data of SIRT7 in patients with breast cancer were analyzed using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interaction Analysis (GEPIA), The Human Protein Atlas (HPA), UALCAN, Breast Cancer Gene-Expression Miner (BC-GenExMiner), and Kaplan-Meier plotter databases. Also, the expression correlations between SIRT7 and immune infiltration gene markers were analyzed using TIMER and further verified the results using immunohistochemistry. Results: SIRT7 exhibited higher expression levels in breast cancer tissues than the adjacent normal tissues. SIRT7 expression was significantly correlated with sample type, subclass, cancer stage, menopause status, age, nodal status, estrogen receptor (ER), progesterone receptor (PR), and triple-negative status. High SIRT7 expression was associated with poor prognosis in breast cancer-luminal A [overall survival (OS): hazard ratio (HR) = 1.54, p = 1.70e-02; distant metastasis-free survival (DMFS): HR = 1.56, p = 2.60e-03]. Moreover, the expression of SIRT7 was positively correlated with the expression of IRF5 (M1 macrophages marker, r = 0.165, p = 1.13e-04) and PD1 (T cell exhaustion marker, r = 0.134, p = 1.74e-03). These results suggested that the expression of SIRT7 was related to M1 macrophages and T cell exhaustion infiltration in breast cancer-luminal. Conclusions: These findings demonstrate that the high expression of SIRT7 indicates poor prognosis in breast cancer as well as increased immune infiltration levels of M1 macrophages and T cell exhaustion in breast cancer-luminal. Thus, SIRT7 may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in breast cancer-luminal.

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Dataset Information

EVI2B Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration.

Publications

<i>EVI2B</i> Is a New Prognostic Biomarker in Metastatic Melanoma with IFNgamma Associated Immune Infiltration.

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