Purpose

Integrins, transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions, have been linked to several cancer-associated features. A less explored function of integrins in cancer is their role in leukocyte homing and activation. Understanding their relationship with immune cell infiltrates and immune checkpoints is an area of interest in cancer research.

Methods

The expression of 33 different integrins was evaluated in relation with breast cancer patient outcome using transcriptomic data (Affymetrix dataset, exploratory cohort) and the METABRIC study (validation cohort). The TIMER online tool was used to assess the association of the identified integrin genes with immune cell infiltration, and the TCGA and METABRIC studies to assess correlations between integrin gene expression and genomic signatures of immune activation.

Results

We identified 7 genes coding for integrin α and β subunits, i.e., ITGA4, ITGB2, ITGAX, ITGB7, ITGAM, ITGAL and ITGA8, which predict a favorable prognosis in Basal-like and HER2+ breast cancers. Their expression positively correlated with the presence of immune cell infiltrates within the tumor (dendritic cells, CD4+ T-cells, neutrophils, CD8+ T-cells and B-cells), with markers of T-cell activation and antigen presentation, and with gene signatures of immune surveillance (cytotoxic T lymphocyte activation and IFN gamma signature). By contrast, we found that genes coding for integrins that predicted a detrimental outcome (IBSP, ITGB3BP, ITGB6, ITGB1 and ITGAV) were not associated with any of these parameters.

Conclusions

We identified an integrin signature composed of 7 genes with potential to recognize immune infiltrated and activated Basal-like and HER2+ breast cancers with a favorable prognosis.

中文翻译：

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整合素和免疫激活在基底样和 HER2+ 乳腺癌中的计算机转录组图谱

目的

整合素是介导细胞-细胞外基质和细胞-细胞相互作用的跨膜受体，与多种癌症相关特征有关。整合素在癌症中的一个较少探索的功能是它们在白细胞归巢和激活中的作用。了解它们与免疫细胞浸润和免疫检查点的关系是癌症研究的一个感兴趣的领域。

方法

使用转录组数据（Affymetrix 数据集，探索性队列）和 METABRIC 研究（验证队列）评估了 33 种不同整合素的表达与乳腺癌患者预后的关系。TIMER 在线工具用于评估已识别的整合素基因与免疫细胞浸润的关联，以及 TCGA 和 METABRIC 研究以评估整合素基因表达与免疫激活的基因组特征之间的相关性。

结果

我们鉴定了 7 个编码整合素 α 和 β 亚基的基因，即ITGA4、ITGB2、ITGAX、ITGB7、ITGAM、ITGAL和ITGA8，它们预测基底样和 HER2+ 乳腺癌的良好预后。它们的表达与肿瘤内免疫细胞浸润的存在（树突细胞、CD4+ T 细胞、中性粒细胞、CD8+ T 细胞和 B 细胞）、T 细胞活化和抗原呈递的标志物以及基因特征呈正相关免疫监视（细胞毒性 T 淋巴细胞激活和 IFN γ 特征）。相比之下，我们发现编码预测有害结果的整合素的基因（IBSP、ITGB3BP、ITGB6、ITGB1和ITGAV）与这些参数中的任何一个都无关。

结论

我们确定了一个由 7 个基因组成的整合素特征，这些基因具有识别免疫浸润和激活的基底样和 HER2+ 乳腺癌的潜力，预后良好。