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Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma

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Abstract

Nanog, a key transcription factor in self-renewal and pluripotency of embryonic stem cells, has been proved to play a novel role in solid tumor development. Here, we investigated Nanog protein expression in retrospective clinical samples of 105 patients underwent resective surgery for gastric adenocarcinoma. We found that Nanog protein immunostaining in tumor tissues was stronger than that in their corresponding non-dysplastic tissues. However, no statistical difference of Nanog protein expression between tumor tissues and metastatic lymph nodes was found (P = 0.143). Interestingly, overexpression of Nanog protein was correlated with advanced clinical stage of patients with gastric adenocarcinoma (P = 0.006). And Nanog protein expression was correlated with lymph node status (P = 0.004), infiltrating extent (P = 0.001), and differentiation (P = 0.000) of patients with gastric adenocarcinoma. Survival analysis showed that overexpression of Nanog protein in gastric cancer patients predicted a poorer prognosis (P = 0.000). Our data first demonstrated a potential diagnostic and prognostic role of Nanog for gastric adenocarcinoma.

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References

  1. Echem R. Gastric cancer is a major cause of cancer death. Niger J Med. 2003;12:175–6.

    PubMed  Google Scholar 

  2. Gruvberger SK, Ringner M, Eden P, Borg A, Ferno M, et al. Expression profiling to predict outcome in breast cancer: the influence of sample selection. Breast Cancer Res. 2003;5:23–6.

    Article  PubMed  CAS  Google Scholar 

  3. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  4. Gruvberger-Saal SK, Cunliffe HE, Carr KM, Hedenfalk IA. Microarrays in breast cancer research and clinical practice–the future lies ahead. Endocr Relat Cancer. 2006;13:1017–31.

    Article  PubMed  CAS  Google Scholar 

  5. Smith MG, Hold GL, Tahara E, El-Omar EM. Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 2006;12:2979–90.

    PubMed  CAS  Google Scholar 

  6. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 2005;122:947–56.

    Article  PubMed  CAS  Google Scholar 

  7. Chambers I, Colby D, Robertson M, Nichols J, Lee S, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113:643–55.

    Article  PubMed  CAS  Google Scholar 

  8. Jerevall PL, Brommesson S, Strand C, Gruvberger-Saal S, Malmstrom P, et al. Exploring the two-gene ratio in breast cancer–independent roles for HOXB13 and IL17BR in prediction of clinical outcome. Breast Cancer Res Treat. 2008;107:225–34.

    Article  PubMed  CAS  Google Scholar 

  9. Linderholm BK, Gruvberger-Saal S, Ferno M, Bendahl PO, Malmstrom P. Vascular endothelial growth factor is a strong predictor of early distant recurrences in a prospective study of premenopausal women with lymph-node negative breast cancer. Breast. 2008;17:484–91.

    Article  PubMed  Google Scholar 

  10. Seigel GM, Hackam AS, Ganguly A, Mandell LM, Gonzalez-Fernandez F. Human embryonic and neuronal stem cell markers in retinoblastoma. Mol Vis. 2007;13:823–32.

    PubMed  CAS  Google Scholar 

  11. Santagata S, Ligon KL, Hornick JL. Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. Am J Surg Pathol. 2007;31:836–45.

    Article  PubMed  Google Scholar 

  12. Gu G, Yuan J, Wills M, Kasper S. Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res. 2007;67:4807–15.

    Article  PubMed  CAS  Google Scholar 

  13. Freberg CT, Dahl JA, Timoskainen S, Collas P. Epigenetic reprogramming of OCT4 and NANOG regulatory regions by embryonal carcinoma cell extract. Mol Biol Cell. 2007;18:1543–53.

    Article  PubMed  CAS  Google Scholar 

  14. Hoei-Hansen CE, Kraggerud SM, Abeler VM, Kaern J, Rajpert-De Meyts E. Ovarian dysgerminomas are characterised by frequent KIT mutations and abundant expression of pluripotency markers. Mol Cancer. 2007;6:12.

    Article  PubMed  Google Scholar 

  15. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.

    Article  PubMed  CAS  Google Scholar 

  16. Meng HM, Zheng P, Wang XY, Liu C, Sui HM, et al. Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther. 2010;9:295–302.

    Article  CAS  Google Scholar 

  17. Hart AH, Hartley L, Parker K, Ibrahim M, Looijenga LH, et al. The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Cancer. 2005;104:2092–8.

    Article  PubMed  CAS  Google Scholar 

  18. Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003;113:631–42.

    Article  PubMed  CAS  Google Scholar 

  19. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.

    Article  PubMed  CAS  Google Scholar 

  20. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  PubMed  CAS  Google Scholar 

  21. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451:141–6.

    Article  PubMed  CAS  Google Scholar 

  22. Pan G, Thomson JA. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res. 2007;17:42–9.

    Article  PubMed  CAS  Google Scholar 

  23. Pereira L, Yi F, Merrill BJ. Repression of Nanog gene transcription by Tcf3 limits embryonic stem cell self-renewal. Mol Cell Biol. 2006;26:7479–91.

    Article  PubMed  CAS  Google Scholar 

  24. Suzuki A, Raya A, Kawakami Y, Morita M, Matsui T, et al. Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification. Nat Clin Pract Cardiovasc Med. 2006;3:114–22.

    Article  Google Scholar 

  25. Ezeh UI, Turek PJ, Reijo RA, Clark AT. Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer. 2005;104:2255–65.

    Article  PubMed  CAS  Google Scholar 

  26. Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, et al. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells. 2009;27:993–1005.

    Article  PubMed  CAS  Google Scholar 

  27. Xu RH, Sampsell-Barron TL, Gu F, Root S, Peck RM, Pan G, et al. NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs. Cell Stem Cell. 2008;3:196–206.

    Article  PubMed  CAS  Google Scholar 

  28. Stock M, Otto F. Gene deregulation in gastric cancer. Gene. 2005;360:1–19.

    Article  PubMed  CAS  Google Scholar 

  29. Shinto O, Yashiro M, Kawajiri H, Shimizu K, Shimizu T, et al. Inhibitory effect of a TGF beta receptor type-I inhibitor, Ki26894, on invasiveness of scirrhous gastric cancer cells. Br J Cancer. 2010;102:844–51.

    Article  PubMed  CAS  Google Scholar 

  30. Wang Z, Xu H, Wang S, Chen J. Relationship between new TNM classification and the prognosis and biological behavior of gastric cancer. Zhonghua Wai Ke Za Zhi. 2000;38:493–5.

    PubMed  CAS  Google Scholar 

  31. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  PubMed  CAS  Google Scholar 

  32. Strosberg JR, Nasir A, Hodul P, Kvols L. Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2008;2:113–25.

    PubMed  Google Scholar 

  33. Ye F, Zhou C, Cheng Q, Shen J, Chen H. Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer. 2008;8:108.

    Article  PubMed  Google Scholar 

  34. Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2008;14:4085–95.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Ting Lin, Yan-Qing Ding & Jian-Ming Li

  2. Department of First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Ting Lin, Yan-Qing Ding & Jian-Ming Li

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  1. Ting Lin
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  2. Yan-Qing Ding
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Correspondence to Jian-Ming Li.

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Lin, T., Ding, YQ. & Li, JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol 29, 878–885 (2012). https://doi.org/10.1007/s12032-011-9860-9

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  • DOI: https://doi.org/10.1007/s12032-011-9860-9

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