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Erschienen in: Medical Oncology 2/2012

01.06.2012 | Original Paper

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

verfasst von: Ting Lin, Yan-Qing Ding, Jian-Ming Li

Erschienen in: Medical Oncology | Ausgabe 2/2012

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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.
Literatur
1.
Zurück zum Zitat Echem R. Gastric cancer is a major cause of cancer death. Niger J Med. 2003;12:175–6.PubMed Echem R. Gastric cancer is a major cause of cancer death. Niger J Med. 2003;12:175–6.PubMed
2.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
3.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
4.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
5.
Zurück zum Zitat Smith MG, Hold GL, Tahara E, El-Omar EM. Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 2006;12:2979–90.PubMed Smith MG, Hold GL, Tahara E, El-Omar EM. Cellular and molecular aspects of gastric cancer. World J Gastroenterol. 2006;12:2979–90.PubMed
6.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
9.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
10.
Zurück zum Zitat 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 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
11.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
12.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
15.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
16.
Zurück zum Zitat 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.CrossRef 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.CrossRef
17.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
18.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
19.
Zurück zum Zitat Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.PubMedCrossRef Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.PubMedCrossRef
20.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
21.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
22.
Zurück zum Zitat Pan G, Thomson JA. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res. 2007;17:42–9.PubMedCrossRef Pan G, Thomson JA. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res. 2007;17:42–9.PubMedCrossRef
23.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
24.
Zurück zum Zitat 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.CrossRef 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.CrossRef
25.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
26.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
27.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
29.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
30.
Zurück zum Zitat 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 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
32.
Zurück zum Zitat Strosberg JR, Nasir A, Hodul P, Kvols L. Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2008;2:113–25.PubMed Strosberg JR, Nasir A, Hodul P, Kvols L. Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2008;2:113–25.PubMed
33.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
34.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
Metadaten
Titel
Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma
verfasst von
Ting Lin
Yan-Qing Ding
Jian-Ming Li
Publikationsdatum
01.06.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9860-9

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