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SNAI家族在乳腺癌和免疫细胞中的作用分析

Analysis of the Effect of SNAI Family in Breast Cancer and Immune Cell.

作者信息

Tu Yifei, Fang Pengfei, Zhang Long, Sun Kewang

机构信息

MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China.

General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.

出版信息

Front Cell Dev Biol. 2022 Jul 8;10:906885. doi: 10.3389/fcell.2022.906885. eCollection 2022.

Abstract

SNAI family members are transcriptional repressors that induce epithelial-mesenchymal transition during biological development. SNAIs both have tumor-promoting and tumor-inhibiting effect. There are key regulatory effects on tumor onset and development, and patient prognosis in infiltrations of immune cell and tumor microenvironmental changes. However, the relationships between SNAIs and immune cell infiltration remain unclear. We comprehensively analyzed the roles of SNAIs in cancer. We used Oncomine and TCGA data to analyze pan-cancer transcript levels. By analyzing UALCAN data, we found correlations between transcript levels and breast cancer patient characteristics. Kaplan-Meier plotter analysis revealed that SNAI1 and SNAI2 have a bad prognosis, whereas SNAI3 is the opposite. Analysis using the cBio Cancer Genomics Portal revealed alterations in SNAIs in breast cancer subtypes. Gene Ontology analysis and gene set enrichment analysis were used to analyze differentially expressed genes related to SNAI proteins in breast cancer. We used TIMER to analyze the effects of transcript levels, mutations, methylation levels, and gene copy number in the infiltration of immune cell. Further, we found the relationships between immune cell infiltration, SNAI expression levels, and patient outcomes. To explore how SNAI proteins affect immune cell, we further studied the correlations between immunomodulator expression, chemokine expression, and SNAI expression. The results showed that SNAI protein levels were correlated with the expression of several immunomodulators and chemokines. Through analysis of PharmacoDB data, we identified antitumor drugs related to SNAI family members and analyzed their IC50 effects on various breast cancer cell lines. In summary, our study revealed that SNAI family members regulate different immune cells infiltrations by gene copy number, mutation, methylation, and expression level. SNAI3 and SNIA1/2 have opposite regulatory effects. They all play a key role in tumor development and immune cell infiltration, and can provide a potential target for drug therapy.

摘要

SNAI家族成员是转录抑制因子,在生物发育过程中诱导上皮-间质转化。SNAI既有促肿瘤作用,也有抑肿瘤作用。在免疫细胞浸润和肿瘤微环境变化方面,对肿瘤的发生、发展及患者预后具有关键的调控作用。然而,SNAI与免疫细胞浸润之间的关系仍不清楚。我们全面分析了SNAI在癌症中的作用。我们使用Oncomine和TCGA数据来分析泛癌转录水平。通过分析UALCAN数据,我们发现了转录水平与乳腺癌患者特征之间的相关性。Kaplan-Meier绘图仪分析显示,SNAI1和SNAI2预后不良,而SNAI3则相反。使用cBio癌症基因组学门户进行的分析揭示了乳腺癌亚型中SNAI的改变。基因本体分析和基因集富集分析用于分析乳腺癌中与SNAI蛋白相关的差异表达基因。我们使用TIMER来分析转录水平、突变、甲基化水平和基因拷贝数在免疫细胞浸润中的作用。此外,我们发现了免疫细胞浸润、SNAI表达水平与患者预后之间的关系。为了探究SNAI蛋白如何影响免疫细胞,我们进一步研究了免疫调节剂表达、趋化因子表达与SNAI表达之间的相关性。结果表明,SNAI蛋白水平与几种免疫调节剂和趋化因子的表达相关。通过对PharmacoDB数据的分析,我们确定了与SNAI家族成员相关的抗肿瘤药物,并分析了它们对各种乳腺癌细胞系的IC50效应。总之,我们的研究表明,SNAI家族成员通过基因拷贝数、突变、甲基化和表达水平调节不同免疫细胞的浸润。SNAI3与SNIA1/2具有相反的调节作用。它们在肿瘤发展和免疫细胞浸润中均发挥关键作用,并可为药物治疗提供潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0dc/9309217/10b2e0b7a5a2/fcell-10-906885-g001.jpg

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