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
2831 - Interleukin-6 as a Predictive Marker for Early Response to Induction Chemotherapy in Acute Myeloblastic Leukaemia
Presenter: Salah Khallaf
Session: Poster Display session 1
Resources:
Abstract
6014 - Impact of FLT3-ITD mutation on post-transplant outcome of adult AML is modified by the concomitant NPM1 mutation and pre-transplant remission status: A report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Presenter: Su-peng Yeh
Session: Poster Display session 1
Resources:
Abstract
2914 - Efficacy endpoints studied in clinical trials for early-onset leukaemia
Presenter: Dylan Said
Session: Poster Display session 1
Resources:
Abstract
4691 - High triglyceride is a major risk factor of DIC and differentiation syndrome in acute promyelocytic leukemia
Presenter: Tomohiro Yamakawa
Session: Poster Display session 1
Resources:
Abstract
4395 - DREAMM 4: A Phase I/II single-arm open-label study to explore safety and clinical activity of belantamab mafodotin (GSK2857916) administered in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM)
Presenter: Suzanne Trudel
Session: Poster Display session 1
Resources:
Abstract
2808 - A Phase 1 Study of HMPL-523, a Selective Oral Anti-Spleen Tyrosine Kinase Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Nathan Fowler
Session: Poster Display session 1
Resources:
Abstract
4403 - A Phase 1 Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Patients with Relapsed or Refractory Lymphoma
Presenter: Jonathon Cohen
Session: Poster Display session 1
Resources:
Abstract
3357 - A global patient-driven Facebook study in a very rare sarcoma: Health-related quality of life in Epithelioid Hemangioendothelioma (EHE) patients
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
2475 - Qualitative study of patients’ experiences of living with and beyond a soft tissue sarcoma diagnosis: the impact of sarcoma specialist services
Presenter: Ana Martins
Session: Poster Display session 1
Resources:
Abstract
2640 - Health-related quality of life issues of patients affected by desmoid-type fibromatosis; experiences from two countries
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract