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

被引:52
作者
Tanabe, Shihori [1 ]
Aoyagi, Kazuhiko [2 ]
Yokozaki, Hiroshi [3 ]
Sasaki, Hiroki [2 ]
机构
[1] Natl Inst Hlth Sci, Setagaya Ku, Div Safety Informat Drug Food & Chem, Tokyo 1588501, Japan
[2] Natl Canc Ctr, Res Inst, Dept Translat Oncol, Chuo Ku, Tokyo 1040045, Japan
[3] Kobe Univ, Grad Sch Med, Dept Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan
关键词
epithelial-mesenchymal transition; microarray; mesenchymal stem cell; gastric cancer; gene expression; STEM-CELLS; HEDGEHOG; SOX2; TUMOR; LUNG;
D O I
10.3892/ijo.2014.2387
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1955 / 1970
页数:16
相关论文
共 28 条
[1]   Artificially Induced Epithelial-Mesenchymal Transition in Surgical Subjects: Its Implications in Clinical and Basic Cancer Research [J].
Aoyagi, Kazuhiko ;
Minashi, Keiko ;
Igaki, Hiroyasu ;
Tachimori, Yuji ;
Nishimura, Takao ;
Hokamura, Norikazu ;
Ashida, Akio ;
Daiko, Hiroyuki ;
Ochiai, Atsushi ;
Muto, Manabu ;
Ohtsu, Atsushi ;
Yoshida, Teruhiko ;
Sasaki, Hiroki .
PLOS ONE, 2011, 6 (04)
[2]   SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas [J].
Bass, Adam J. ;
Watanabe, Hideo ;
Mermel, Craig H. ;
Yu, Soyoung ;
Perner, Sven ;
Verhaak, Roel G. ;
Kim, So Young ;
Wardwell, Leslie ;
Tamayo, Pablo ;
Gat-Viks, Irit ;
Ramos, Alex H. ;
Woo, Michele S. ;
Weir, Barbara A. ;
Getz, Gad ;
Beroukhim, Rameen ;
O'Kelly, Michael ;
Dutt, Amit ;
Rozenblatt-Rosen, Orit ;
Dziunycz, Piotr ;
Komisarof, Justin ;
Chirieac, Lucian R. ;
LaFargue, Christopher J. ;
Scheble, Veit ;
Wilbertz, Theresia ;
Ma, Changqing ;
Rao, Shilpa ;
Nakagawa, Hiroshi ;
Stairs, Douglas B. ;
Lin, Lin ;
Giordano, Thomas J. ;
Wagner, Patrick ;
Minna, John D. ;
Gazdar, Adi F. ;
Zhu, Chang Qi ;
Brose, Marcia S. ;
Cecconello, Ivan ;
Ribeiro, Ulysses, Jr. ;
Marie, Suely K. ;
Dahl, Olav ;
Shivdasani, Ramesh A. ;
Tsao, Ming-Sound ;
Rubin, Mark A. ;
Wong, Kwok K. ;
Regev, Aviv ;
Hahn, William C. ;
Beer, David G. ;
Rustgi, Anil K. ;
Meyerson, Matthew .
NATURE GENETICS, 2009, 41 (11) :1238-U105
[3]   The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression [J].
Cano, A ;
Pérez-Moreno, MA ;
Rodrigo, I ;
Locascio, A ;
Blanco, MJ ;
del Barrio, MG ;
Portillo, F ;
Nieto, MA .
NATURE CELL BIOLOGY, 2000, 2 (02) :76-83
[4]   NANOG-dependent function of TET1 and TET2 in establishment of pluripotency [J].
Costa, Yael ;
Ding, Junjun ;
Theunissen, Thorold W. ;
Faiola, Francesco ;
Hore, Timothy A. ;
Shliaha, Pavel V. ;
Fidalgo, Miguel ;
Saunders, Arven ;
Lawrence, Moyra ;
Dietmann, Sabine ;
Das, Satyabrata ;
Levasseur, Dana N. ;
Li, Zhe ;
Xu, Mingjiang ;
Reik, Wolf ;
Silva, Jose C. R. ;
Wang, Jianlong .
NATURE, 2013, 495 (7441) :370-374
[5]   Gene Expression Omnibus: NCBI gene expression and hybridization array data repository [J].
Edgar, R ;
Domrachev, M ;
Lash, AE .
NUCLEIC ACIDS RESEARCH, 2002, 30 (01) :207-210
[6]   Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells [J].
Elenbaas, B ;
Spirio, L ;
Koerner, F ;
Fleming, MD ;
Zimonjic, DB ;
Donaher, JL ;
Popescu, NC ;
Hahn, WC ;
Weinberg, RA .
GENES & DEVELOPMENT, 2001, 15 (01) :50-65
[7]   Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer [J].
Fukaya, Masahide ;
Isohata, Noriyuki ;
Ohta, Hiroyuki ;
Aoyagi, Kazuhiko ;
Ochiya, Takahiro ;
Saeki, Norihisa ;
Yanagihara, Kazuyoshi ;
Nakanishi, Yukihiro ;
Taniguchi, Hirokazu ;
Sakamoto, Hiromi ;
Shimoda, Tadakazu ;
Nimura, Yuji ;
Yoshida, Teruhiko ;
Sasaki, Hiroki .
GASTROENTEROLOGY, 2006, 131 (01) :14-29
[8]   Mechanics of Epithelial Tissue Homeostasis and Morphogenesis [J].
Guillot, Charlene ;
Lecuit, Thomas .
SCIENCE, 2013, 340 (6137) :1185-1189
[9]   Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening [J].
Gupta, Piyush B. ;
Onder, Tamer T. ;
Jiang, Guozhi ;
Tao, Kai ;
Kuperwasser, Charlotte ;
Weinberg, Robert A. ;
Lander, Eric S. .
CELL, 2009, 138 (04) :645-659
[10]   In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration [J].
Huch, Meritxell ;
Dorrell, Craig ;
Boj, Sylvia F. ;
van Es, Johan H. ;
Li, Vivian S. W. ;
van de Wetering, Marc ;
Sato, Toshiro ;
Hamer, Karien ;
Sasaki, Nobuo ;
Finegold, Milton J. ;
Haft, Annelise ;
Vries, Robert G. ;
Grompe, Markus ;
Clevers, Hans .
NATURE, 2013, 494 (7436) :247-250