Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

Tanabe,Shihori; Aoyagi,Kazuhiko; Yokozaki,Hiroshi; Sasaki,Hiroki

doi:10.3892/ijo.2014.2387

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

Authors:
- Shihori Tanabe
- Kazuhiko Aoyagi
- Hiroshi Yokozaki
- Hiroki Sasaki
View Affiliations

Affiliations: Division of Safety Information on Drug, Food and Chemicals, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan, Department of Translational Oncology, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan, Department of Pathology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan
Published online on: April 11, 2014 https://doi.org/10.3892/ijo.2014.2387
Pages: 1955-1970

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Epithelial-mesenchymal transition (EMT) is associated with tumor malignancy. The hedgehog-EMT pathway is preferentially activated in diffuse-type gastric cancer (GC) compared with intestinal-type GC; however, histological typing is currently the only method for distinguishing these two major types of GC. We compared the gene expression profiles of 12 bone marrow-derived mesenchymal stem cell cultures and 5 diffuse-type GC tissue samples. Numerous upregulated or downregulated genes were identified in diffuse-type GC, including CDH1, CDH2, VIM, WNT4 and WNT5. Among these genes, the mRNA ratio of CDH2 to CDH1 could distinguish the 15 diffuse-type GC samples from the 17 intestinal-type GC samples. Our results suggested that the mesenchymal features were more prominent in diffuse-type GC than in intestinal-type GC, but were weaker in diffuse-type GC than in mesenchymal stem cells. Diffuse-type GC that has undergone extensive EMT, which has a poor prognosis, can be identified by quantitative PCR analysis of only two genes.

View Figures

View References

1.	Radisky DC and LaBarge MA: Epithelial-mesenchymal transition and the stem cell phenotype. Cell Stem Cell. 2:511–512. 2008. View Article : Google Scholar : PubMed/NCBI
2.	Mani SA, Guo W, Liao MJ, et al: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 133:704–715. 2008. View Article : Google Scholar : PubMed/NCBI
3.	Vogelstein B, Papadopoulos N, Velculescu VE, et al: Cancer genome landscapes. Science. 339:1546–1558. 2013. View Article : Google Scholar : PubMed/NCBI
4.	Saeki N, Saito A, Choi IJ, et al: A functional single nucleotide polymorphism in mucin 1, at chromosome 1q22, determines susceptibility to diffuse-type gastric cancer. Gastroenterology. 140:892–902. 2011. View Article : Google Scholar : PubMed/NCBI
5.	Sakamoto H, Yoshimura K, Saeki N, et al: Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet. 40:730–740. 2008. View Article : Google Scholar : PubMed/NCBI
6.	Fukaya M, Isohata N, Ohta H, et al: Hedgehog signal activ ation in gastric pit cell and in diffuse-type gastric cancer. Gastroenterology. 131:14–29. 2006. View Article : Google Scholar
7.	Ohta H, Aoyagi K, Fukaya M, et al: Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers. Br J Cancer. 100:389–398. 2009. View Article : Google Scholar
8.	Ueda T, Volinia S, Okumura H, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 11:136–146. 2010. View Article : Google Scholar : PubMed/NCBI
9.	Kountouras J, Zavos C and Chatzopoulos D: New concepts of molecular biology on gastric carcinogenesis. Hepatogastroenterology. 52:1305–1312. 2005.PubMed/NCBI
10.	Tanabe S, Sato Y, Suzuki T, et al: Gene expression profiling of human mesenchymal stem cells for identification of novel markers in early- and late-stage cell culture. J Biochem. 144:399–408. 2008. View Article : Google Scholar : PubMed/NCBI
11.	Aoyagi K, Minashi K, Igaki H, et al: Artificially induced epithelial-mesenchymal transition in surgical subjects: its implications in clinical and basic cancer research. PLoS One. 6:e181962011. View Article : Google Scholar : PubMed/NCBI
12.	Edgar R, Domrachev M and Lash AE: Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30:207–210. 2002. View Article : Google Scholar : PubMed/NCBI
13.	Sigurdsson V, Hilmarsdottir B, Sigmundsdottir H, et al: Endothelial induced EMT in breast epithelial cells with stem cell properties. PLoS One. 6:e238332011. View Article : Google Scholar : PubMed/NCBI
14.	Guillot C and Lecuit T: Mechanics of epithelial tissue homeostasis and morphogenesis. Science. 340:1185–1189. 2013. View Article : Google Scholar : PubMed/NCBI
15.	Gupta PB, Onder TT, Jiang G, et al: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 138:645–659. 2009. View Article : Google Scholar : PubMed/NCBI
16.	Elenbaas B, Spirio L, Koemer F, et al: Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Gene Dev. 15:50–65. 2001. View Article : Google Scholar : PubMed/NCBI
17.	Lu D, Choi MY, Yu J, et al: Salinomycin inhibits Wnt signaling and selectivity induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci USA. 108:13253–13257. 2011. View Article : Google Scholar : PubMed/NCBI
18.	Huch M, Dorrell C, Boj SF, et al: In vitro expansion of single Lgr5⁺ liver stem cells induced by Wnt-driven regeneration. Nature. 494:247–250. 2013. View Article : Google Scholar
19.	Nishimura K, Semba S, Aoyagi K, et al: Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells. Pathobiology. 79:290–306. 2012. View Article : Google Scholar : PubMed/NCBI
20.	Rudin CM, Durinck S, Stawiski EW, et al: Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 44:1111–1116. 2012. View Article : Google Scholar : PubMed/NCBI
21.	Jia X, Li X, Xu Y, et al: SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell. J Mol Cell Biol. 3:230–238. 2011. View Article : Google Scholar : PubMed/NCBI
22.	Bass AJ, Watanabe H, Mermel CH, et al: SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 41:1238–1242. 2009. View Article : Google Scholar : PubMed/NCBI
23.	Costa Y, Ding J, Theunissen TW, et al: NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature. 495:370–374. 2013. View Article : Google Scholar : PubMed/NCBI
24.	Isohata N, Aoyagi K, Mabuchi T, et al: Hedgehog and epithelialmesenchymal transition signaling in normal and malignant epithelial cells of the esophagus. Int J Cancer. 125:1212–1221. 2009. View Article : Google Scholar : PubMed/NCBI
25.	Cano A, Pérez-Moreno MA, Rodrigo I, et al: The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2:76–83. 2000. View Article : Google Scholar : PubMed/NCBI
26.	Sato T and Clevers H: Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science. 340:1190–1194. 2013. View Article : Google Scholar : PubMed/NCBI
27.	Schepers AG, Snippert HJ, Stange DE, et al: Lineage tracing reveals Lgr5⁺ stem cell activity in mouse intestinal adenomas. Science. 337:730–735. 2012. View Article : Google Scholar : PubMed/NCBI
28.	Nakanishi Y, Seno H, Fukuoka A, et al: Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 45:98–103. 2013. View Article : Google Scholar : PubMed/NCBI