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基于整合生物信息学分析鉴定 EDIL3 作为犬乳腺浸润性癌的生物标志物及潜在治疗靶点

英文原题:Identification of EDIL3 biomarkers as a biomarker and potential therapeutic target of canine mammary carcinomas based on integrated bioinformatics analysis.

查看英文原题

Identification of EDIL3 biomarkers as a biomarker and potential therapeutic target of canine mammary carcinomas based on integrated bioinformatics analysis.

PubMed 2022/05/06(内容时间) Vet Immunol Immunopathol Q2 · IF 1.8(JCR 2025)

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中文摘要

随着与癌症的激烈斗争如今扩展到伴侣动物,犬乳腺 carcinoma(CMT)作为未绝育犬中最常诊断的肿瘤,其有效治疗正成为一个关键问题。尽管已开展许多关于乳腺肿瘤生物标志物临床应用的研究,但在 CMT 中尚未鉴定出理想的生物标志物。

因此,在本研究中,我们将 EDIL3 开发为一种 CMT 生物标志物,其在 GSE13754、GSE22516 和 GSE25586 数据集中 CMT 样本中的表达水平显著高于对照样本,这表明 EDIL3 是一个与肿瘤发生相关的基因。

我们还利用我们的犬测序样本验证了 EDIL3 在 CMT 样本中的显著高表达水平。ROC 曲线分析显示,与报道为 CMT 患者预测因子的 HER2 相比,EDIL3 在识别 CMT 方面表现出更强的能力。

此外,我们还发现 EDIL3 的低表达水平与 CMT 的晚期分级状态相关,这表明 EDIL3 与 CMT 发展之间呈负相关。采用 GSEA 揭示 EDIL3 在 CMT 发展中这一有趣功能的潜在机制,结果表明 EDIL3 的表达水平与免疫通路相关。

最后,本研究采用 CIBERSORT 分析以进一步探索 EDIL3 与 CMT 中免疫之间的关系,结果揭示 EDIL3 在 CMT 中与滤泡辅助性 T 细胞呈稳定正相关,与 NK 静息细胞呈负相关。

我们的研究将EDIL3开发为辅助CMT鉴别的生物标志物,突出EDIL3与滤泡辅助性T细胞和NK静息细胞浸润的关系,这可能成为CMT的新潜在治疗靶点,并为后续临床实验验证提供生物信息学基础。

展开英文摘要原文

As the fierce battle with cancer is now expanding to companion animals, effective treatment of canine mammary carcinomas (CMT), as the most frequently diagnosed tumor in intact dogs, is becoming a crucial issue. Although many studies have been carried out concerning the clinical application of mammary tumor biomarkers, no ideal biomarker has yet been identified in CMT.

Therefore, in this work, we develop EDIL3 as a CMT biomarker having significantly higher expression levels in CMT samples compared to those in controls in GSE13754, GSE22516 and GSE25586 datasets, which suggest that EDIL3 is a gene related to tumorigenesis.

We also validate the significantly high expression levels of EDIL3 in CMT samples using our sequencing canine samples. ROC curves analysis showed that in comparison with HER2 reported as predictive factor for CMT patients, EDIL3 exhibits stronger power for CMT recognizing.

Moreover, we also find that low expression levels of EDIL3 are associated with advanced grade status in CMT, which indicate a negative correlation between EDIL3 and CMT development. GSEA is employed to unveil the underlying mechanism of this interesting function of EDIL3 in CMT development, and it suggests that the expression level of EDIL3 is related to immunity pathway.

Finally, CIBERSORT analysis is employed in this study in order to further explore the relationship between EDIL3 and immunity in CMT, and it unveils that EDIL3 has stably positive correlation with follicular helper T cells and negative correlation with NK resting cells in CMT.

Our study develops EDIL3 as a biomarker for assisting CMT distinction, highlighting the relationship of EDIL3 with the infiltrations of follicular helper T cells and NK resting cells, which could be a new potential therapy target for CMT and provide bioinformatics basis for later clinical experiment validation.

论文信息

作者
Lin Z、Jiang C、Lv D、Lin D
第一作者单位
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, China.China
通讯作者单位
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, China. Electronic address: ldgcau@sina.com.China
期刊
Veterinary immunology and immunopathology2022 Jul
原文标识
PubMed 35550248 · DOI 10.1016/j.vetimm.2022.110432