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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 a higher incidence of metastases. Increased expression of MMP-9 is associated with higher incidence of metastasis. Only lymph node, lymphovascular invasion and lung metastases reached the level of statistical significance when compared to patients with low MMP-9 expression. Chi-square test was realized with Yates’ continuity correction and a two-sided Fisher exact test were performed to analyze metastases.
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Fig6: Overexpression of MMP-9 is associated with a higher incidence of metastases. Increased expression of MMP-9 is associated with higher incidence of metastasis. Only lymph node, lymphovascular invasion and lung metastases reached the level of statistical significance when compared to patients with low MMP-9 expression. Chi-square test was realized with Yates’ continuity correction and a two-sided Fisher exact test were performed to analyze metastases.

Mentions: We next investigated whether elevated levels of MMP-9 protein expression in carcinoma cells could predict the occurrence of metastases, relapse and poor survival rates. To that end, we reviewed the clinical charts of 200 patients for the period extending from 2000 to 2013. Out of 200 Patients, 121 (60.5%) patients have high MMP-9 expression and 79 (39.5%) pateints have low MMP-9 expression. Increased levels of MMP-9 were found to be associated with a higher incidence of metastasis (Figure 6). The results were considered significant when the percentage of patients who developed metastases significantly differed in terms of low and high levels of MMP-9 expression. Only lymph node (p < 0.001), lymphovascular invasion (p = 0.007) and lung metastasis (p = 0.001) reached statistical significance when compared to patients with low MMP-9 expression. Additional file 1 indicates the distribution of high and low MMP-9 expression in patients with and without metastases.Figure 6


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 a higher incidence of metastases. Increased expression of MMP-9 is associated with higher incidence of metastasis. Only lymph node, lymphovascular invasion and lung metastases reached the level of statistical significance when compared to patients with low MMP-9 expression. Chi-square test was realized with Yates’ continuity correction and a two-sided Fisher exact test were performed to analyze metastases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: Overexpression of MMP-9 is associated with a higher incidence of metastases. Increased expression of MMP-9 is associated with higher incidence of metastasis. Only lymph node, lymphovascular invasion and lung metastases reached the level of statistical significance when compared to patients with low MMP-9 expression. Chi-square test was realized with Yates’ continuity correction and a two-sided Fisher exact test were performed to analyze metastases.
Mentions: We next investigated whether elevated levels of MMP-9 protein expression in carcinoma cells could predict the occurrence of metastases, relapse and poor survival rates. To that end, we reviewed the clinical charts of 200 patients for the period extending from 2000 to 2013. Out of 200 Patients, 121 (60.5%) patients have high MMP-9 expression and 79 (39.5%) pateints have low MMP-9 expression. Increased levels of MMP-9 were found to be associated with a higher incidence of metastasis (Figure 6). The results were considered significant when the percentage of patients who developed metastases significantly differed in terms of low and high levels of MMP-9 expression. Only lymph node (p < 0.001), lymphovascular invasion (p = 0.007) and lung metastasis (p = 0.001) reached statistical significance when compared to patients with low MMP-9 expression. Additional file 1 indicates the distribution of high and low MMP-9 expression in patients with and without metastases.Figure 6

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