Title
In silico transcriptomic mapping of integrins and immune activation in Basal-like and HER2+ breast cancer
Date Issued
01 June 2021
Access level
metadata only access
Resource Type
journal article
Author(s)
Baliu-Piqué M.
Manzano A.
Saiz-Ladera C.
García-Barberán V.
Cimas F.J.
Pérez-Segura P.
Pandiella A.
Győrffy B.
Ocana A.
Instituto de Investigación Sanitaria (IdISSC)
Publisher(s)
Springer Science and Business Media B.V.
Abstract
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.
Start page
569
End page
580
Volume
44
Issue
3
Language
English
OCDE Knowledge area
Oncología Biotecnología relacionada con la salud
Scopus EID
2-s2.0-85100140233
PubMed ID
Source
Cellular Oncology
ISSN of the container
22113428
Sponsor(s)
Fundación Científica Asociación Española Contra el Cáncer. Ministerio de Economía y Competitividad: BFU2015-71371-R. Instituto de Salud Carlos III: PI19/00808, RD12/0036/0003. Centro de Investigación Biomédica en Red de Cáncer.
Sources of information: Directorio de Producción Científica Scopus