Y-box binding protein 1 is correlated with lymph node metastasis in intestinal-type gastric cancer
TianTian Guo
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorYingNan Yu
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorGeorge Wai-Cheong Yip
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorGyeong Hun Baeg
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorAye Aye Thike
Department of Pathology, Singapore General Hospital, Singapore, Singapore
Search for more papers by this authorTony Kiat-Hon Lim
Department of Pathology, Singapore General Hospital, Singapore, Singapore
Search for more papers by this authorPuay Hoon Tan
Department of Pathology, Singapore General Hospital, Singapore, Singapore
Search for more papers by this authorKen Matsumoto
Molecular Entomology Laboratory, The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan
Search for more papers by this authorCorresponding Author
Boon Huat Bay
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Address for correspondence: Boon-Huat Bay, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117 597, Singapore.
e-mail: [email protected]
Search for more papers by this authorTianTian Guo
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorYingNan Yu
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorGeorge Wai-Cheong Yip
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorGyeong Hun Baeg
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Search for more papers by this authorAye Aye Thike
Department of Pathology, Singapore General Hospital, Singapore, Singapore
Search for more papers by this authorTony Kiat-Hon Lim
Department of Pathology, Singapore General Hospital, Singapore, Singapore
Search for more papers by this authorPuay Hoon Tan
Department of Pathology, Singapore General Hospital, Singapore, Singapore
Search for more papers by this authorKen Matsumoto
Molecular Entomology Laboratory, The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan
Search for more papers by this authorCorresponding Author
Boon Huat Bay
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Address for correspondence: Boon-Huat Bay, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117 597, Singapore.
e-mail: [email protected]
Search for more papers by this authorAbstract
Aims
Y-box binding protein-1 (YB-1) is known to modulate gene transcription and protein translation, as well as cellular response to drug treatment. The aim of this study is to correlate YB-1 protein expression levels with clinicopathological parameters in intestinal-type gastric cancer tissue samples (as categorized by the Lauren classification) and substantiate the findings with in vitro experimentation.
Methods and results
Paraffin-embedded samples from 167 patients with intestinal-type gastric cancer were used for the construction of tissue microarrays (TMAs). TMA slides were immunostained and YB-1 immunoreactivity score was based on the weighted average intensity score. Univariate analysis revealed that YB-1 immunohistochemical expression was correlated significantly with lymph node status (P = 0.054, borderline significance) and perforation (P = 0.043). YB-1 expression was also found to be an independent predictor of lymph node spread by multivariate analysis. Furthermore, siRNA-mediated YB-1 gene knockdown in MKN7 gastric cancer cells (which is known to originate from an intestinal-type gastric cancer tissue) inhibited cell migration (P = 0.0002) and invasion in vitro (P = 0.0129) significantly.
Conclusion
YB-1 expression is associated with lymph node spread in intestinal-type gastric cancer and is a potential prognostic biomarker in this subtype of gastric cancer.
Supporting Information
Filename | Description |
---|---|
his12570-sup-0001-FigS1.tifimage/tif, 2.1 MB | Figure S1. Western blot showing the specificity of the YB-1 antibody detecting a specific protein band with a molecular weight between 35-55 kDa. |
his12570-sup-0002-TableS1.docxWord document, 15.7 KB | Table S1. Clinicopathological features of gastric cancer patients. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Thiel A, Ristimäki A. Gastric cancer: basic aspects. Helicobacter 2012; 17(Suppl. 1); 26–29.
- 2Ajani JA, Bentrem DJ, Besh S et al. Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines. J. Natl. Compr. Canc. Netw. 2013; 11; 531–546.
- 3Wayman J, Forman D, Griffin SM. Monitoring the changing pattern of esophago-gastric cancer: data from a UK regional cancer registry. Cancer Causes Control 2001; 12; 943–949.
- 4Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin. Microbiol. Rev. 2010; 23; 713–739.
- 5Weeks DL, Eskandari S, Scott DR, Sachs G. A H+ -gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science 2000; 287; 482–485.
- 6Bilici A. Treatment options in patients with metastatic gastric cancer: current status and future perspectives. World J. Gastroenterol. 2014; 20; 3905–3915.
- 7Yoong J, Michael M, Leong T. Targeted therapies for gastric cancer: current status. Drugs 2011; 71; 1367–1384.
- 8Ting JP, Painter A, Zeleznik-Le NJ et al. YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes. J. Exp. Med. 1994; 179; 1605–1611.
- 9Stenina OI, Poptic EJ, DiCorleto PE. Thrombin activates a Y box-binding protein (DNA-binding protein B) in endothelial cells. J. Clin. Invest. 2000; 106; 579–587.
- 10Yu YN, Yip GW, Tan PH et al. Y-box binding protein 1 is up-regulated in proliferative breast cancer and its inhibition deregulates the cell cycle. Int. J. Oncol. 2010; 37; 483–492.
- 11Giménez-Bonafé P, Fedoruk MN, Whitmore TG et al. YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activity. Prostate 2004; 59; 337–349.
- 12Jürchott K, Kuban RJ, Krech T et al. Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway-dependent gene signatures in colorectal cancer cells. PLoS Genet. 2010; 6; e1001231.
- 13Lasham A, Moloney S, Hale T et al. The Y-box-binding protein, YB1, is a potential negative regulator of the p53 tumor suppressor. J. Biol. Chem. 2003; 278; 35516–35523.
- 14Lasham A, Samuel W, Cao H et al. YB-1, the E2F pathway, and regulation of tumor cell growth. J. Natl Cancer Inst. 2012; 104; 133–146.
- 15Chatterjee M, Rancso C, Stühmer T et al. The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma. Blood 2008; 111; 3714–3722.
- 16Guo TT, Yu YN, Yip GW, Matsumoto K, Bay BH. Silencing the YB-1 gene inhibits cell migration in gastric cancer in vitro. Anat. Rec. (Hoboken) 2013; 296; 891–898.
- 17Wu Y, Yamada S, Izumi H et al. Strong YB-1 expression is associated with liver metastasis progression and predicts shorter disease-free survival in advanced gastric cancer. J. Surg. Oncol. 2012; 105; 724–730.
- 18Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta. Pathol. Microbiol. Scand. 1965; 64; 31–49.
- 19Tay WL, Yip GW, Tan PH et al. Y-box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer. Mod. Pathol. 2009; 22; 282–290.
- 20van Rees BP, Sivula A, Thorén S et al. Expression of microsomal prostaglandin E synthase-1 in intestinal type gastric adenocarcinoma and in gastric cancer cell lines. Int. J. Cancer 2003; 107; 551–556.
- 21Lwin ZM, Guo C, Salim A et al. Clinicopathological significance of calreticulin in breast invasive ductal carcinoma. Mod. Pathol. 2010; 23; 1559–1566.
- 22Kabashima A, Yao T, Suqimachi K, Tsuneyoshi M. Relationship between biologic behavior and phenotypic expression in intramucosal gastric carcinomas. Hum. Pathol. 2002; 33; 80–86.
- 23Cuello C, López J, Correa P, Murray J, Zarama G, Gordillo G. Histopathology of gastric dysplasias: correlations with gastric juice chemistry. Am. J. Surg. Pathol. 1979; 3; 491–500.
- 24Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann. Surg. 2005; 241; 27–39.
- 25Kim SW, Kim HC, Yang DM. Perforated tumours in the gastrointestinal tract: CT findings and clinical implications. Br. J. Radiol. 2012; 85; 1307–1313.
- 26Finkbeiner MR, Astanehe A, To K et al. Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells. Oncogene 2009; 28; 1421–1431.
- 27Basaki Y, Hosoi F, Oda Y et al. Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells. Oncogene 2007; 26; 2736–2746.
- 28Toyokawa T, Yashiro M, Hirakawa K. Co-expression of keratinocyte growth factor and K-sam is an independent prognostic factor in gastric carcinoma. Oncol. Rep. 2009; 21; 875–880.
- 29Kitadai Y, Haruma K, Sumii K et al. Expression of interleukin-8 correlates with vascularity in human gastric carcinomas. Am. J. Pathol. 1998; 152; 93–100.
- 30Nagashima N, Nakayama Y, Inoue Y et al. Prognostic significance of the local expression of interleukin-12 in patients with advanced gastric cancer. Anticancer Res. 2008; 28; 1277–1283.
- 31Tanner M, Hollmén M, Junttila TT et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann. Oncol. 2005; 16; 273–278.
- 32Lee J, Seo JW, Jun HJ et al. Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol. Rep. 2011; 25; 1517–1524.
- 33Nakajima M, Sawada H, Yamada Y et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 1999; 85; 1894–1902.
10.1002/(SICI)1097-0142(19990501)85:9<1894::AID-CNCR3>3.0.CO;2-J CAS PubMed Web of Science® Google Scholar
- 34Ha SY, Lee J, Kang SY et al. MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas. Mod. Pathol. 2013; 26; 1632–1641.
- 35Yasui W, Oue N, Kuniyasu H, Ito R, Tahara E, Yokozaki H. Molecular diagnosis of gastric cancer: present and future. Gastric Cancer 2001; 4; 113–121.
- 36Yokozaki H, Yasui W, Tahara E. Genetic and epigenetic changes in stomach cancer. Int. Rev. Cytol. 2001; 204; 49–95.
- 37Jung JH, Kim HJ, Yeom J et al. Lowered expression of galectin-2 is associated with lymph node metastasis in gastric cancer. J. Gastroenterol. 2012; 47; 37–48.