Yousif A Kariri1,2, Mansour Alsaleem1, Chitra Joseph1, Sami Alsaeed1, Abrar Aljohani1, Sho Shiino1, Omar J Mohammed1, Michael S Toss1, Andrew R Green1, Emad A Rakha3,4. 1. Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, NG7 2RD, UK. 2. Department of Laboratory Medical Science, Faculty of Applied Medical Science, Shaqra University, Shaqra, Saudi Arabia. 3. Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, NG7 2RD, UK. Emad.Rakha@nottingham.ac.uk. 4. Department of Histopathology, Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, NG5 1PB, UK. Emad.Rakha@nottingham.ac.uk.
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.
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.
Entities:
Keywords:
Breast cancer; ISG15; Interferon-stimulated gene 15; Prognosis; Progression
Authors: Mansour Alsaleem; Michael S Toss; Chitra Joseph; Mohammed Aleskandarany; Sasagu Kurozumi; Ibrahim Alshankyty; Angela Ogden; Padmashree C G Rida; Ian O Ellis; Ritu Aneja; Andrew R Green; Nigel P Mongan; Emad A Rakha Journal: Mod Pathol Date: 2019-02-13 Impact factor: 7.842
Authors: Jun-Bao Fan; Sayuri Miyauchi-Ishida; Kei-ichiro Arimoto; Dan Liu; Ming Yan; Chang-Wei Liu; Balázs Győrffy; Dong-Er Zhang Journal: Proc Natl Acad Sci U S A Date: 2015-10-29 Impact factor: 11.205
Authors: Min Ni; Yiwen Chen; Elgene Lim; Hallie Wimberly; Shannon T Bailey; Yuuki Imai; David L Rimm; X Shirley Liu; Myles Brown Journal: Cancer Cell Date: 2011-07-12 Impact factor: 31.743
Authors: H R Ali; E Provenzano; S-J Dawson; F M Blows; B Liu; M Shah; H M Earl; C J Poole; L Hiller; J A Dunn; S J Bowden; C Twelves; J M S Bartlett; S M A Mahmoud; E Rakha; I O Ellis; S Liu; D Gao; T O Nielsen; P D P Pharoah; C Caldas Journal: Ann Oncol Date: 2014-06-09 Impact factor: 32.976
Authors: Yousif Kariri; Michael S Toss; Mansour Alsaleem; Khloud A Elsharawy; Chitra Joseph; Nigel P Mongan; Andrew R Green; Emad A Rakha Journal: Breast Cancer Res Treat Date: 2022-02-06 Impact factor: 4.872
Authors: Irena Voinsky; Yazeed Zoabi; Noam Shomron; Moria Harel; Hanoch Cassuto; Joseph Tam; Shannon Rose; Adrienne C Scheck; Mohammad A Karim; Richard E Frye; Adi Aran; David Gurwitz Journal: Int J Mol Sci Date: 2022-08-30 Impact factor: 6.208
Authors: Jose L Mondaza-Hernandez; David S Moura; María Lopez-Alvarez; Paloma Sanchez-Bustos; Elena Blanco-Alcaina; Carolina Castilla-Ramirez; Paola Collini; Jose Merino-Garcia; Jorge Zamora; Jaime Carrillo-Garcia; Roberta Maestro; Nadia Hindi; Jesus Garcia-Foncillas; Javier Martin-Broto Journal: Cell Mol Life Sci Date: 2022-07-21 Impact factor: 9.207