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.
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.
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
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
All authors have declared no conflicts of interest.