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非编码RNA介导的铁死亡相关基因EMC2过表达与乳腺癌预后不良及肿瘤免疫浸润相关。

The ncRNA-Mediated Overexpression of Ferroptosis-Related Gene EMC2 Correlates With Poor Prognosis and Tumor Immune Infiltration in Breast Cancer.

作者信息

Liu Xing, Yang Pengshuo, Han Lu, Zhou Qing, Qu Qingsong, Shi Xinyuan

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

School of Life Science, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Oncol. 2021 Dec 8;11:777037. doi: 10.3389/fonc.2021.777037. eCollection 2021.

Abstract

Ferroptosis is an iron-dependent programmed cell death process. Although ferroptosis inducers hold promising potential in the treatment of breast cancer, the specific role and mechanism of the ferroptosis-related gene in breast cancer have not been entirely determined. The potential roles of in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Tumor Immune Estimation Resource (TIMER), Shiny Methylation Analysis Resource Tool (SMART), starBase, and cBioPortal for cancer genomics (cBioPortal) datasets. The expression difference, mutation, survival, pathological stage, DNA methylation, non-coding RNAs (ncRNAs), and immune cell infiltration related to were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the differences in biological processes and functions among different related genes. The expression levels of core prognostic genes were then verified in breast invasive carcinoma samples using immunohistochemistry and breast invasive carcinoma cell lines using real-time polymerase chain reaction. High expression levels of were observed in most cancer types. expression in breast cancer tissue samples correlated with poor overall survival. was mutated and methylated in a variety of tumors and affected survival. The LINC00665-miR-410-3p axis was identified as the most potential upstream ncRNA-related pathway of in breast cancer. levels were significantly positively correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. Our study offers a comprehensive understanding of the oncogenic roles of across different tumors. The upregulation of expression mediated by ncRNAs is related to poor prognosis and tumor immune infiltration in breast cancer.

摘要

铁死亡是一种铁依赖性程序性细胞死亡过程。尽管铁死亡诱导剂在乳腺癌治疗中具有广阔前景,但铁死亡相关基因在乳腺癌中的具体作用和机制尚未完全明确。基于癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)、基因表达谱交互式分析2(GEPIA2)、肿瘤免疫评估资源(TIMER)、闪亮甲基化分析资源工具(SMART)、starBase以及癌症基因组学cBioPortal数据集,探讨了[该基因名称未给出]在不同肿瘤中的潜在作用。分析了与[该基因名称未给出]相关的表达差异、突变、生存、病理分期、DNA甲基化、非编码RNA(ncRNA)以及免疫细胞浸润情况。进行了基因本体(GO)和京都基因与基因组百科全书(KEGG)分析,以确定不同相关基因在生物学过程和功能上的差异。随后,使用免疫组织化学在乳腺浸润癌样本中以及使用实时聚合酶链反应在乳腺浸润癌细胞系中验证了核心预后基因的表达水平。在大多数癌症类型中均观察到[该基因名称未给出]的高表达水平。[该基因名称未给出]在乳腺癌组织样本中的表达与总体生存率较差相关。[该基因名称未给出]在多种肿瘤中发生突变和甲基化,并影响生存。LINC00665-miR-410-3p轴被确定为乳腺癌中[该基因名称未给出]最具潜力的上游ncRNA相关途径。[该基因名称未给出]水平与肿瘤免疫细胞浸润、免疫细胞生物标志物以及免疫检查点表达显著正相关。我们的研究全面了解了[该基因名称未给出]在不同肿瘤中的致癌作用。ncRNAs介导的[该基因名称未给出]表达上调与乳腺癌预后不良和肿瘤免疫浸润有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2964/8692298/142f7a2b8062/fonc-11-777037-g001.jpg

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