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Medical Oncology

, 32:433 | Cite as

Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer

  • Ning Li
  • Wenying Deng
  • Jie Ma
  • Bing Wei
  • Kang Guo
  • Wei Shen
  • Yanping Zhang
  • Suxia Luo
Original Paper

Abstract

The purpose of this study was to evaluate expression and prognostic impact of Nanog, Oct4, Sox2, proliferation cell nuclear antigen (PCNA), Ki67 and E-cadherin in patients with gastric cancer (GC) by immunohistochemistry. A total of 69 patients were recruited who underwent gastrectomy between 2008 and 2009. We found that expression levels of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin were 26.1, 53.6, 49.3, 52.2, 60.9 and 60.9 %, respectively. Co-expression of more than any two proteins (defined as high-risk group) was detected in 43 of 69 (62.3 %) patients with GC. Only positive expression of Oct4 had relationship with lymphatic invasion (p = 0.013), and positive expression of Ki67 was correlated with T classification (p = 0.011). Furthermore, positive expression of Oct4 (p = 0.043), PCNA (p = 0.035) and Ki67 (p = 0.023) was significantly associated with poor 3-year disease-free survival (DFS). The same result was detected in patients with E-cadherin reduced expression (p = 0.022). But only PCNA positive expression predicted poor overall survival (p = 0.042) in univariate analysis. In addition, 3-year DFS was 20 % in high-risk group and 71 % in low-risk group. The same tendency was found between OS and co-expression of proteins. There was a remarkable difference between DFS or OS and co-expression of more than two proteins (p = 0.000). Multivariate analysis showed that E-cadherin and co-expression were independent prognostic factors of 3-year diseases-free survival. But only co-expression of more than two markers dramatically affected the survival of GC patients. These findings provide evidence that combined evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin may be a more powerful prognostic factor to predict relapse and distant metastasis for patients with GC.

Keywords

Gastric cancer Cancer stem cells PCNA Ki67 E-cadherin Prognosis 

Notes

Acknowledgments

The authors would like to thank all patients for their cooperation. This study was supported by grants from the National Natural Science Foundation of China (No. 81470287) and the National Natural Science Foundation of China (No. 81370661).

Conflict of interest

The authors declared no potential conflicts of interest in this work.

References

  1. 1.
    Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, et al. Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 2014;50(7):1330–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, et al. Treatment of gastric cancer. World J Gastroenterol. 2014;20(7):1635–49.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Xu G, Shen J, Ou Yang X, Sasahara M, Su X. Cancer stem cells: the ‘heartbeat’ of gastric cancer. J Gastroenterol. 2013;48(7):781–97.PubMedCrossRefGoogle Scholar
  4. 4.
    Shien K, Toyooka S, Ichimura K, Soh J, Furukawa M, Maki Y, et al. Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer. 2012;77(1):162–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang Z, Oron E, Nelson B, Razis S, Ivanova N. Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells. Cell Stem Cell. 2012;10(4):440–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008;40(5):499–507.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Luo W, Li S, Peng B, Ye Y, Deng X, Yao K. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma. PLoS One. 2013;8(2):e56324.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Hollier BG, Evans K, Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia. 2009;14(1):29–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Steinestel K, Eder S, Schrader AJ, Steinestel J. Clinical significance of epithelial-mesenchymal transition. Clin Transl Med. 2014;3:17.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    He X, Chen Z, Fu T, Jin X, Yu T, Liang Y, et al. Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis. BMC Cancer. 2014;14:153.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Kanaji S, Saito H, Tsujitani S, Matsumoto S, Tatebe S, Kondo A, et al. Expression of polo-like kinase 1 (PLK1) protein predicts the survival of patients with gastric carcinoma. Oncology. 2006;70(2):126–33.PubMedCrossRefGoogle Scholar
  12. 12.
    Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010;11(2):174–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Wang SC. PCNA: a silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci. 2014;35(4):178–86.PubMedCrossRefGoogle Scholar
  14. 14.
    Wang L, Ma J, Liu F, Yu Q, Chu G, Perkins AC, et al. Expression of MUC1 in primary and metastatic human epithelial ovarian cancer and its therapeutic significance. Gynecol Oncol. 2007;105(3):695–702.PubMedCrossRefGoogle Scholar
  15. 15.
    Matsuoka J, Yashiro M, Sakurai K, Kubo N, Tanaka H, Muguruma K, et al. Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma. J Surg Res. 2012;174(1):130–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Hayashi A, Yashima K, Takeda Y, Sasaki S, Kawaguchi K, Harada K, et al. Fhit, E-cadherin, p53, and activation-induced cytidine deaminase expression in endoscopically resected early stage esophageal squamous neoplasia. J Gastroenterol Hepatol. 2012;27(11):1752–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Mateoiu C, Pirici A, Bogdan F. Immunohistochemical nuclear staining for p53, PCNA, Ki-67 and bcl-2 in different histologic variants of basal cell carcinoma. Rom J Morphol Embryol. 2011;52(1 Suppl):315–9.PubMedGoogle Scholar
  18. 18.
    Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label randomised controlled trial. Lancet. 2012;379(9813):315–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253–61.PubMedCrossRefGoogle Scholar
  20. 20.
    Chen Z, Xu WR, Qian H, Zhu W, Bu XF, Wang S, et al. Oct4, a novel marker for human gastric cancer. J Surg Oncol. 2009;99(7):414–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Lin T, Ding YQ, Li JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012;29(2):878–85.PubMedCrossRefGoogle Scholar
  22. 22.
    Zhan YY, He JP, Chen HZ, Wang WJ, Cai JC. Orphan receptor TR3 is essential for the maintenance of stem-like properties in gastric cancer cells. Cancer Lett. 2013;329(1):37–44.PubMedCrossRefGoogle Scholar
  23. 23.
    Nishii T, Yashiro M, Shinto O, Sawada T, Ohira M, Hirakawa K. Cancer stem cell-like SP cells have a high adhesion ability to the peritoneum in gastric carcinoma. Cancer Sci. 2009;100(8):1397–402.PubMedCrossRefGoogle Scholar
  24. 24.
    Ji W, Jiang Z. Effect of shRNA-mediated inhibition of Nanog gene expression on the behavior of human gastric cancer cells. Oncol Lett. 2013;6(2):367–74.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Xing X, Tang YB, Yuan G, Wang Y, Wang J, Yang Y, et al. The prognostic value of E-cadherin in gastric cancer: a meta-analysis. Int J Cancer. 2013;132(11):2589–96.PubMedCrossRefGoogle Scholar
  26. 26.
    Czyzewska J, Guzińska-Ustymowicz K, Pryczynicz A, Kemona A, Bandurski R. Immunohistochemical evaluation of Ki-67, PCNA and MCM2 proteins proliferation index (PI) in advanced gastric cancer. Folia Histochem Cytobiol. 2009;47(2):289–96.PubMedCrossRefGoogle Scholar
  27. 27.
    Grossi F, Loprevite M, Chiaramondia M, Ceppa P, Pera C, Ratto GB, et al. Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers. Eur J Cancer. 2003;39(9):1242–50.PubMedCrossRefGoogle Scholar
  28. 28.
    Dworakowska D, Gózdz S, Jassem E, Badzio A, Kobierska G, Urbaniak A, et al. Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer. Lung Cancer. 2002;35(1):35–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Jin X, Zhu Z, Shi Y. Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis. Bull Cancer. 2014;101(1):E1–12.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ning Li
    • 1
  • Wenying Deng
    • 1
  • Jie Ma
    • 2
  • Bing Wei
    • 2
  • Kang Guo
    • 1
  • Wei Shen
    • 1
  • Yanping Zhang
    • 1
  • Suxia Luo
    • 1
  1. 1.Department of Medical Oncology, Henan Cancer Hospital, Cancer Hospital Affiliated Zhengzhou UniversityZhengzhou UniversityZhengzhouChina
  2. 2.Department of Pathology, Henan Cancer Hospital, Cancer Hospital Affiliated Zhengzhou UniversityZhengzhou UniversityZhengzhouChina

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