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预后标志物 IL-8 的表达与乳腺癌中的免疫特征和上皮-间充质转化相关。

Expression of the prognostic marker IL-8 correlates with the immune signature and epithelial-mesenchymal transition in breast cancer.

机构信息

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.

出版信息

J Clin Lab Anal. 2023 Feb;37(3):e24797. doi: 10.1002/jcla.24797. Epub 2023 Feb 1.

Abstract

BACKGROUND

IL-8 has been implicated in the malignant progression of various types of cancers; however, the precise molecular mechanisms associated with IL-8 in breast cancer (BRCA) are unclear.

METHODS

We analyzed the clinical signature and immune characteristics of BRCA patients and its correlation with IL-8 expression using The Cancer Genome Atlas (TCGA) datasets. The role of IL-8 in epithelial-mesenchymal transition (EMT) was verified through Western blotting, Cell Counting Kit-8 assay, and wound healing assays, as well as cell invasion experiments.

RESULTS

Through a comprehensive bioinformatics study, we determined that high IL-8 expression was associated with poor prognosis. Enrichment analysis revealed that high IL-8 expression was enriched in immune-related processes and cancer-related signaling pathways. In addition, IL-8 was associated with most of the immune-infiltrating cells, and high IL-8 expression indicated poor response to immunotherapy. Importantly, we found that IL-8 induced EMT in vitro.

CONCLUSIONS

Taken together, our data indicate that IL-8 may be a potential and valuable prognostic marker in BRCA, which may induce adverse outcomes by modulating the immune response and promoting EMT in BRCA patients.

摘要

背景

白细胞介素 8(IL-8)已被牵涉到多种类型癌症的恶性进展中;然而,与乳腺癌(BRCA)中 IL-8 相关的确切分子机制尚不清楚。

方法

我们使用癌症基因组图谱(TCGA)数据集分析了 BRCA 患者的临床特征和免疫特征及其与 IL-8 表达的相关性。通过 Western blot、细胞计数试剂盒-8 检测、划痕愈合实验和细胞侵袭实验验证了 IL-8 在上皮-间充质转化(EMT)中的作用。

结果

通过全面的生物信息学研究,我们确定高 IL-8 表达与预后不良有关。富集分析显示,高 IL-8 表达富集在免疫相关过程和癌症相关信号通路中。此外,IL-8 与大多数免疫细胞浸润有关,高 IL-8 表达表明对免疫治疗的反应不佳。重要的是,我们发现 IL-8 在体外诱导 EMT。

结论

综上所述,我们的数据表明,IL-8 可能是 BRCA 中一个有潜力和有价值的预后标志物,它可能通过调节免疫反应和促进 BRCA 患者的 EMT 来诱导不良后果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/9978063/2a3d1bf7f757/JCLA-37-e24797-g003.jpg

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