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A Key Genomic Subtype Associated with Lymphovascular Invasion in Invasive Breast Cancer

Kurozumi, Sasagu; Joseph, Chitra; Alsaeed, Sami; Kariri, Yousif; Aljohani, Abrar; Raafat, Sara; Alsaleem, Mansour; Ogden, Angela; Johnston, Simon; Aleskandarany, Mohammed A; Fujii, Takaaki; Shirabe, Ken; Caldas, Carlos; Ashankyty, Ibraheem; Dalton, Leslie; Ellis, Ian O; Desmedt, Christine; Green, Andrew R; Mongan, Nigel P; Rakha, Emad A

Authors

Sasagu Kurozumi

Sami Alsaeed

Yousif Kariri

Abrar Aljohani

Sara Raafat

Mansour Alsaleem

Angela Ogden

Simon Johnston

Mohammed A Aleskandarany

Takaaki Fujii

Ken Shirabe

Carlos Caldas

Ibraheem Ashankyty

Leslie Dalton

Christine Desmedt

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



Abstract

Background: Lymphovascular invasion (LVI) is associated with the development of metastasis in invasive breast cancer (BC). However, the complex molecular mechanisms of LVI, which overlap with other oncogenic pathways, remain unclear. This study, using available large transcriptomic datasets, aims to identify genes associated with LVI in early-stage BC patients.
Methods: Gene expression data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1565) was used as a discovery dataset, and The Cancer Genome Atlas (TCGA; n = 854) cohort was used as a validation dataset. Key genes were identified on the basis of differential mRNA expression with respect to LVI status as characterized by histological review. The relationships among LVI-associated genomic subtype, clinicopathological features and patient outcomes were explored.
Results: A 99-gene set was identified that demonstrated significantly different expression between LVI-positive and LVI-negative cases. Clustering analysis with this gene set further divided cases into two molecular subtypes (subtypes 1 and 2), which were significantly associated with pathology-determined LVI status in both cohorts. The 10-year overall survival of subtype 2 was significantly worse than that of subtype 1.
Conclusion: This study demonstrates that LVI in BC is associated with a specific transcriptomic profile with potential prognostic value.

Journal Article Type Article
Publication Date Jun 11, 2019
Journal British Journal of Cancer
Print ISSN 0007-0920
Electronic ISSN 1532-1827
Publisher Cancer Research UK
Peer Reviewed Peer Reviewed
Volume 120
Issue 12
Pages 1129–1136
APA6 Citation Kurozumi, S., Joseph, C., Alsaeed, S., Kariri, Y., Aljohani, A., Raafat, S., …Rakha, E. A. (2019). A Key Genomic Subtype Associated with Lymphovascular Invasion in Invasive Breast Cancer. British Journal of Cancer, 120(12), 1129–1136. https://doi.org/10.1038/s41416-019-0486-6
DOI https://doi.org/10.1038/s41416-019-0486-6
Keywords invasive breast cancer, lymphovascular invasion, gene signature
Publisher URL https://www.nature.com/articles/s41416-019-0486-6
Additional Information Received: 30 November 2018; Revised: 24 April 2019; Accepted: 2 May 2019; First Online: 22 May 2019; : Ibraheem Alshankyty is a consultant/advisory board in Molecular Diagnostics Lab, College of Applied Med. Sci., KAU. The remaining authors declare no competing interests.; : This study was approved by the Nottingham Research Ethics Committee 2 (Reference title: Development of a molecular genetic classification of breast cancer). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.; : This work was supported by the University of Nottingham (Nottingham Life Cycle 6).; : The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.; : This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

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