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鉴定 GTPase IMAP 家族为乳腺癌肿瘤微环境中的免疫相关预后生物标志物。

Identification of the GTPase IMAP family as an immune-related prognostic biomarker in the breast cancer tumor microenvironment.

机构信息

Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China.

The Fifth People's Hospital of Qinghai Province, The Second Ward of Oncology, Xining 810000, China.

出版信息

Gene. 2022 Feb 20;812:146094. doi: 10.1016/j.gene.2021.146094. Epub 2021 Dec 9.

DOI:10.1016/j.gene.2021.146094
PMID:34896519
Abstract

INTRODUCTION

Breast cancer is the most common malignancy threatening women's health worldwide. The GTPase IMAP family genes are proteins belonging to the immune-associated nucleotide subfamily of the GTP-binding superfamily and nucleotide-binding proteins. However, little is known about the role of different GTPase IMAP family genes in breast cancer.

METHODS

We obtained differential genes from the GEPIA and UALCAN databases and then used the Kaplan-Meier plotter, The Human Protein Atlas, NetworkAnalyst, STRING, and TIMER to analyze the prognostic value, protein expression, and immune cell infiltration of the GTPase IMAP family in patients with breast cancer.

RESULTS

Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly low in breast tumor tissues. In the overall population, patients with high expression of all genes of the GIMAP family had a significantly higher overall survival (OS), with the most significant increase correlated with the GIMAP2 gene (hazard ratio [HR] = 0.45, 95% confidence interval [CI], 0.34-0.59, P = 3.1e-09). However, patients with high expression of the GIMAP family genes in triple-negative breast cancer compared to those with low expression had a significant OS benefit, with the most pronounced benefit correlated with the GIMAP2 gene (HR = 0.37, 95% CI, 0.23-0.59, P = 1.4e-05). GIMAP7 and GIMAP8 were significantly upregulated in breast tumor tissues. The expression of genes in different GIMAP families was positively correlated with the infiltration and expression of six immune cell types (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells).

CONCLUSION

This study may provide novel insights into the selection of GIMAP family prognostic biomarkers for breast cancer.

摘要

简介

乳腺癌是全球威胁女性健康的最常见恶性肿瘤。GTPase IMAP 家族基因是属于 GTP 结合超家族免疫相关核苷酸亚家族和核苷酸结合蛋白的蛋白质。然而,人们对不同 GTPase IMAP 家族基因在乳腺癌中的作用知之甚少。

方法

我们从 GEPIA 和 UALCAN 数据库中获得差异基因,然后使用 Kaplan-Meier plotter、The Human Protein Atlas、NetworkAnalyst、STRING 和 TIMER 分析 GTPase IMAP 家族在乳腺癌患者中的预后价值、蛋白表达和免疫细胞浸润。

结果

在 GIMAP 家族基因中,GIMAP1、GIMAP5、GIMAP6、GIMAP7 和 GIMAP8 的表达水平在乳腺癌肿瘤组织中明显降低。在总体人群中,所有 GIMAP 家族基因高表达的患者总生存期(OS)明显较高,其中与 GIMAP2 基因相关性最显著(风险比 [HR] = 0.45,95%置信区间 [CI],0.34-0.59,P = 3.1e-09)。然而,与低表达相比,三阴性乳腺癌患者中 GIMAP 家族基因高表达具有显著的 OS 获益,其中与 GIMAP2 基因相关性最显著(HR = 0.37,95%CI,0.23-0.59,P = 1.4e-05)。GIMAP7 和 GIMAP8 在乳腺癌肿瘤组织中显著上调。不同 GIMAP 家族基因的表达与六种免疫细胞类型(B 细胞、CD4+T 细胞、CD8+T 细胞、巨噬细胞、中性粒细胞和树突状细胞)的浸润和表达呈正相关。

结论

本研究可能为乳腺癌 GIMAP 家族预后生物标志物的选择提供新的见解。

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