Abstract 5939
Background
Matrix metalloproteinases (MMPs) specifically hydrolyze the extracellular matrix proteins. MMPs are inhibited by tissue inhibitors of MMPs (TIMPs). Changes in the expression levels of MMPs and TIMPs have been described in various cancers, including breast cancer (BC).
Methods
We analyzed methylation status of 11 MMP genes (MMP2, MMP11, MMP14, MMP15, MMP16, MMP17, MMP21, MMP23B, MMP24, MMP25, MMP28) and 4 TIMP genes (TIMP1, TIMP2, TIMP3, TIMP4) in 183 BC samples and 183 matched samples of morphologically normal adjacent tissues, 6 BC cell lines (ZR711, HBL100, HS578T, BT474, T47D, MCF7), and 6 autopsy samples of normal breast tissues by methylation sensitive restriction enzyme digestion PCR (MSRE-PCR).
Results
In our collection of BC samples, cancer related abnormal methylation was observed for the MMP2, MMP23B, MMP24, MMP25, and MMP28 genes of the MMPs family (Table). Other MMP genes under study were nonmethylated both in tumors and in normal tissues, as well as the TIMP genes TIMP2 and TIMP3. The promoter regions of TIMP1, TIMP4, MMP14, and MMP21 were found to be constitutively methylated in breast tissues, no matter cancerous or normal. A multiple correspondence analysis demonstrated that nonmethylated status of the promoter regions of MMP2, MMP23B, MMP24, MMP25, MMP28 is associated with lack of HER2 expression. The methylated status of the MMP23B is associated with a higher level (3+) of HER2 expression. Table: MMP genes differentially methylated in BC.Table:
20P MMP genes differentially methylated in BC
Gene | Methylated in BC, % | Methylated in normal breast tissues | Presence (+) or absence (–) of methylation in BC cell lines | |||||
---|---|---|---|---|---|---|---|---|
ZR751 | MCF7 | T47D | BT474 | HBL100 | HS578T | |||
MMP2 | 7,7 (14/183) | 0 | + | + | + | - | - | - |
MMP23B | 17 (31/182) | 0 | + | + | + | - | + | + |
MMP24 | 11,9 (20/168) | 0 | - | - | - | + | + | - |
MMP25 | 15,4 (28/182) | 0 | - | + | + | - | + | - |
MMP28 | 4,9 (9/183) | 0 | + | + | + | + | + | - |
Conclusions
Taken that HER2-positive BC is a more aggressive disease, one can assume that unsuppressed expression of the MMP2, MMP23B, MMP24, MMP25, MMP28 genes allowed by the absence of abnormal methylation of their promoters is characteristic for less aggressive BCs. Legal entity responsible for the study: Research Centre for Medical Genetics. Funding: The research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Research Centre for Medical Genetics.
Funding
Ministry of Science and Higher Education of the Russian Federation.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3336 - Survival outcome of non-small cell lung cancer (NSCLC) patients: Comparing results between the database of the Comprehensive Cancer Center Zürich (CCCZ) and the Epidemiological Cancer Registry Zurich and Zug (KKR)
Presenter: Rolf A. Stahel
Session: Poster Display session 1
Resources:
Abstract
2204 - NORA trial (GECP 15/02): Updated results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Presenter: María Guirado
Session: Poster Display session 1
Resources:
Abstract
1446 - A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators set by principle component analysis
Presenter: Bo Cheng
Session: Poster Display session 1
Resources:
Abstract
1788 - Prognostic and predictive value of 18F-PET/CT on the response to treatment in locally advanced non-small cell lung cancer (NSCLC)
Presenter: Cristina Alfaro Autor
Session: Poster Display session 1
Resources:
Abstract
2299 - Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non small cell lung cancer
Presenter: Abdurrahman Işıkdoğan
Session: Poster Display session 1
Resources:
Abstract
4211 - Predicting the first failure pattern in patients with inoperable local advanced non-small cell lung cancer (LA-NSCLC) receiving definitive chemoradiotherapy: Establishment and internal validation of a nomogram based on the clinicopathological factors
Presenter: Xueru Zhu
Session: Poster Display session 1
Resources:
Abstract
1550 - Prognostic impact of neutrophil-to-lymphocyte ratio (NLR) pre and post chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC)
Presenter: Vicente Palomar Abril
Session: Poster Display session 1
Resources:
Abstract
2345 - Meta-analysis evaluating neutropenia incidence with EGFR inhibitors and chemotherapy in patients with NSCLC
Presenter: Bernardo Rapoport
Session: Poster Display session 1
Resources:
Abstract
3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC
Presenter: Yu Miura
Session: Poster Display session 1
Resources:
Abstract
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract