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
Mohammed A Aleskandarany
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
Andrew R Green
Nigel P Mongan
Emad A Rakha firstname.lastname@example.org
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|
|Publisher||Cancer Research UK|
|Peer Reviewed||Peer Reviewed|
|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|
|Keywords||invasive breast cancer, lymphovascular invasion, gene signature|
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