MMP-9 expression varies according to molecular subtypes of breast cancer.

Einas M Yousef (1) , Muhammad R Tahir (2) , Yves St-Pierre (3) , Louis A Gaboury (1, 4)

1 Institute of Research in Immunology and Cancer
2 CHUM - Centre Hospitalier de l'Université de Montréal
3 INRS-IAF - Institut Armand Frappier
4 Department of Pathology and Cell Biology, Faculty of Medicine

In 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients. MMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays. Significant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse. Differential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.

Mots clés: MMP-9; Human breast cancers; Metastasis; In silico analysis; Tissue microarrays

Domaines: Sciences du Vivant [q-bio]; Cancer

Einas M Yousef, Muhammad R Tahir, Yves St-Pierre, Louis A Gaboury. MMP-9 expression varies according to molecular subtypes of breast cancer.. BMC Cancer, 2014, 14, pp.609. ⟨10.1186/1471-2407-14-609⟩. ⟨pasteur-01137392⟩