The prognostic significance of Interferon Stimulated Gene 15 (ISG15) in invasive breast cancer

Kariri, Yousif; Alsaleem, Mansour; Joseph, Chitra; Alsaeed, Sami; Aljohani, Abrar; Shiino, Sho; Mohammed, OmarJ.; Toss, Michael S; Green, Andrew R; Rakha, Emad A

Abstract

Background

Lymphovascular invasion (LVI) is a prognostic factor in early-stage invasive breast cancer (BC). Through bioinformatics, data analyses of multiple BC cohorts revealed the positive association between interferon-stimulated gene 15 (ISG15) LVI status. Thus, we explored the prognostic significance of ISG15 in BC.
Methods

The prognostic significance of ISG15 mRNA was assessed in METABRIC (n = 1980), TCGA (n = 854) and Kaplan–Meier Plotter (n = 3951). ISG15 protein was evaluated using immunohistochemistry (n = 859) in early-stage invasive BC patients with long-term follow-up. The associations between ISG15 expression and clinicopathological features, expression of immune cell markers and patient outcome data were evaluated.
Results

High mRNA and protein ISG15 expression were associated with LVI, higher histological grade, larger tumour size, hormonal receptor negativity, HER2 positivity, p53 and Ki67. High ISG15 protein expression was associated with HER2-enriched BC subtypes and immune markers (CD8, FOXP3 and CD68). High ISG15 mRNA and ISG15 expressions were associated with poor patient outcome. Cox proportional multivariate analysis revealed that the elevated ISG15 expression was an independent prognostic factor of shorter BC-specific survival.
Conclusion

This study provides evidence for the role of ISG15 in LVI development and BC prognosis. Further functional studies in BC are warranted to evaluate the therapeutic potential of ISG15.

Citation

Kariri, Y., Alsaleem, M., Joseph, C., Alsaeed, S., Aljohani, A., Shiino, S., …Rakha, E. A. (2021). The prognostic significance of Interferon Stimulated Gene 15 (ISG15) in invasive breast cancer. Breast Cancer Research and Treatment, 185(2), 293–305. https://doi.org/10.1007/s10549-020-05955-1

• Journal Article Type: Article
• Acceptance Date: Sep 28, 2020
• Online Publication Date: Oct 19, 2020
• Publication Date: 2021-01
• Deposit Date: Oct 2, 2020
• Publicly Available Date: Oct 20, 2021
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 185
• Issue: 2
• Pages: 293–305
• DOI: https://doi.org/10.1007/s10549-020-05955-1
• Public URL: https://nottingham-repository.worktribe.com/output/4937410
• Publisher URL: https://link.springer.com/article/10.1007/s10549-020-05955-1