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

Yousef EM, Tahir MR, St-Pierre Y, Gaboury LA - BMC Cancer (2014)

Bottom Line: 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.Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada. louis.gaboury@umontreal.ca.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Related in: MedlinePlus

Overexpression of MMP-9 is associated with shorter time to relapse and shorter survival after relapse. (A) High levels of MMP-9 expression are associated with shorter time to relapse (p = 0.014). (B) High levels of MMP-9 expression are associated with shorter survival after relapse (p = 0.04).
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Fig7: Overexpression of MMP-9 is associated with shorter time to relapse and shorter survival after relapse. (A) High levels of MMP-9 expression are associated with shorter time to relapse (p = 0.014). (B) High levels of MMP-9 expression are associated with shorter survival after relapse (p = 0.04).

Mentions: Likewise, when we looked at the association between MMP-9 and relapse, we found that enhanced expression of MMP-9 was associated with a shorter latency to clinical relapse: (Mean time for relapse = 3912 days, n = 121) which is statistically significant (p = 0.014). This contrasts with the values observed in patients with low MMP-9 levels of expression (Mean time for relapse = 4957 days, n = 79) (Figure 7A). However, using a multivariate analysis, histological grades, histological subtypes and molecular subtypes were found to have no impact on relapse in this patient’s population.Figure 7


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

Yousef EM, Tahir MR, St-Pierre Y, Gaboury LA - BMC Cancer (2014)

Overexpression of MMP-9 is associated with shorter time to relapse and shorter survival after relapse. (A) High levels of MMP-9 expression are associated with shorter time to relapse (p = 0.014). (B) High levels of MMP-9 expression are associated with shorter survival after relapse (p = 0.04).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150970&req=5

Fig7: Overexpression of MMP-9 is associated with shorter time to relapse and shorter survival after relapse. (A) High levels of MMP-9 expression are associated with shorter time to relapse (p = 0.014). (B) High levels of MMP-9 expression are associated with shorter survival after relapse (p = 0.04).
Mentions: Likewise, when we looked at the association between MMP-9 and relapse, we found that enhanced expression of MMP-9 was associated with a shorter latency to clinical relapse: (Mean time for relapse = 3912 days, n = 121) which is statistically significant (p = 0.014). This contrasts with the values observed in patients with low MMP-9 levels of expression (Mean time for relapse = 4957 days, n = 79) (Figure 7A). However, using a multivariate analysis, histological grades, histological subtypes and molecular subtypes were found to have no impact on relapse in this patient’s population.Figure 7

Bottom Line: 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.Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Canada. louis.gaboury@umontreal.ca.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus