P-210 - Detection of epithelial-mesenchymal transition in colorectal cancer in consideration of intratumor heterogeneity

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Y. Muto
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors Y. Muto1, K. Suzuki1, K. Ichida1, Y. Takayama1, T. Fukui1, N. Kakizawa2, F. Watanabe1, T. Kato3, M. Saito1, F. Konishi4, T. Rikiyama1
  • 1Jichi Medical University, Saitama-shi/JP
  • 2Jichi Medical University, Saitama/JP
  • 3Jichi Medical Center, Saitama/JP
  • 4Nerima-Hikarigaoka Hospital, Nerima-ku/JP

Abstract

Introduction

While it has been reported that epithelial-mesenchymal transition (EMT) could be implicated in mechanisms underlying tumor metastasis in vivo and in vitro, no evidence was found in clinical settings. Intratumor heterogeneity may lead to underestimate gene expressions to represent EMT in tumor. We investigate EMT-related gene expressions in different regions of the same tumor.

Methods

Seven primary colorectal tumors with distant metastasis, 9 tumors without metastasis and 2 metastatic liver tumors were included. Several pieces were taken from tumor center or invasive front (IF) in each tumor. Using the gene expression array and qRT-PCR, difference in gene expressions between them was investigated, comparing with gene expressions in metastatic liver tumors.

Results

Comparing expressions in EMT-related genes between tumor center and IF, the expressions of genes such as ZEB1, ZEB2, CTDSP1, PRKD1 and MAPK8IP1 were statistically increased. Twist2 tended to show increased expressions. The Snail1 gene expression was higher in IF than those in center, but there's no significance. On the other hands, no EMT associating genes exhibited increased expressions in metastatic liver tumors. To exclude the individual differences, expression ratio between tumor center and IF was calculated and was applied for further comparisons. T-test, comparing expression ratio of tumors with metastasis and without, identified 473 genes. Gene annotation and pathway ontology were performed by using DAVID and KEGG, which revealed that several genes were associated with VEGF signaling pathway, Wnt signaling pathway, Focal adhesion and Axon guidance.

Conclusion

Increased expressions of EMT-related genes were seen in only IF but not in tumor center. This could be involved in the activation of signaling pathways, which enhance the EMT-related gene expressions in IF. These changes were not seen in tumor center, indicating that different gene profiles induced by heterogeneity should be taken into consideration to detect EMT.