1717P - The correlation between MMR gene expression MSH2/MSH6 and VEGF A/VEGF B in gastro-esophageal cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Oesophageal Cancer
Gastric Cancer
Translational Research
Presenter Amelia Dracea
Citation Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391
Authors A. Dracea1, M. Danciulescu2, A. Dricu3, F. Burada1, M. Ioana1
  • 1Human Genomics Laboratory, University of Medicine and Pharmacy of Craiova, 200349 - Craiova/RO
  • 2Department Of Oncology, University of Medicine and Pharmacy of Craiova, 200349 - Craiova/RO
  • 3Unit Of Biochemistry, University of Medicine and Pharmacy of Craiova, 200349 - Craiova/RO

Abstract

Background

VEGF proteins are key regulators of angiogenesis and targeting VEGF A led to inhibition of new blood vessels formation, with important therapeutic effects in various cancers. The roles of VEGF B are controversial; this peptide expression seems to inhibit apoptosis by suppressing many apoptotic/cell death-related genes and to facilitate metastasis by inducing vascular leakiness, leading to a high degree of tissue hypoxia that consequently activates DNA damage signalling pathways. MSH2/MSH6 is an important complex of proteins in DNA mismatch repair system and their altered expression could represent a response to the rapidly growing number of replication errors in a tissue with a high index of proliferation.

Considering that in certain conditions, DNA damage response products, such as H2AX, promote tumor growth and angiogenesis, in the present study we aimed to identify a common pattern of expression behavior between MMR genes MSH2/MSH6 and VEGF components (VEGF A and VEGF B), in order to use these genes as diagnostic markers in gastro-esophageal cancer.

Methods

mRNA levels of MSH2, MSH6, VEGF A, VEGF B were evaluated in tumoral and peritumoral tissues samples biopsied from 36 patients using qRT-PCR with specific TaqMan gene expression assays.

Results

VEGF A/VEGF B and MSH2/MSH6 mRNAs were expressed in both tumour and peritumour mucosa, with a tendency of tumoral up-regulation for VEGF A and MSH2/MSH6. When comparing the differences between tumoral/peritumoral expression level among the studied genes, we found that MMR and VEGF have a similar pattern of expression as follows: VEGF A gene expression correlates with MSH2 (rho Spearman = 0.4562; p 

Conclusions

Our results indicate a possible crosstalk between DNA mismatch repair and VEGF signaling pathways, providing new insight into understanding the potential connection of VEGF B and MSH6 in carcinogenesis.

Clinical trial identification

Legal entity responsible for the study

University of Medicine and Pharmacy of Craiova, Romania

Funding

None

Disclosure

All authors have declared no conflicts of interest.