The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion

Aljohani, Abrar; Alsaeed, Sami; Toss, Michael; Raafat, Sara; GREEN, ANDREW; Rakha, Emad

Abstract

Lymphovascular invasion (LVI) is a common phenomenon in breast cancer (BC), and it is correlated to poor outcome. However, the biomarkers that influence the development of LVI remain to be defined. Through rigorous bioinformatics analyses, high mobility group protein 3 (HMGB3) was revealed as a driver gene that is associated with the presence of LVI. The purpose of this study was to further investigate the role of HMGB3 in the pathogenesis of LVI in BC. In vitro functional assays were performed to investigate the effect of HMGB3 silencing on cell proliferation, migration, adherence and transmigration of BC cell lines with dermal lymphatic endothelial cells (DLECs) and human vascular endothelial cells (HUVECs). The correlation of HMGB3 expression with clinicopathological parameters was also assessed at the transcriptomic and the proteomic levels using large BC cohorts with well-characterised LVI status. Silencing HMGB3 reduced cell proliferation, migration, adherence and transmigration across endothelial cell lines. At the mRNA and protein levels, high HMGB3 expression was significantly correlated with LVI-positivity, higher tumour grade, lymph nodal stage, hormone receptor negativity, HER2 positivity and poor outcome. Moreover, high HMGB3 expression was an independent predictor of shorter breast cancer-specific survival. HMGB3 plays an oncogenic function and contributes to the development of LVI in BC. Results warrant further investigation as a potential target to inhibit LVI in BC.

Citation

Aljohani, A., Alsaeed, S., Toss, M., Raafat, S., GREEN, A., & Rakha, E. (2023). The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion. American Journal of Cancer Research, 13(11), 5334–5351

• Journal Article Type: Article
• Acceptance Date: Sep 14, 2023
• Online Publication Date: Nov 15, 2023
• Publication Date: 2023
• Deposit Date: Sep 19, 2023
• Publicly Available Date: Sep 21, 2023
• Journal: American Journal of Cancer Research
• Electronic ISSN: 2156-6976
• Publisher: e-Century Publishing
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 11
• Pages: 5334–5351
• Public URL: https://nottingham-repository.worktribe.com/output/25362874
• Publisher URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695817/