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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

Chitra Joseph

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

Andrew R Green

Nigel P Mongan

Emad A Rakha emad.rakha@nottingham.ac.uk



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
Print ISSN 0007-0920
Publisher Cancer Research UK
Peer Reviewed Peer Reviewed
Volume 120
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, 1129–1136. doi: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

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