Skip to main content
SpringerLink
Log in

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

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  9. Steinestel K, Eder S, Schrader AJ, Steinestel J. Clinical significance of epithelial-mesenchymal transition. Clin Transl Med. 2014;3:17.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  13. Wang SC. PCNA: a silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci. 2014;35(4):178–86.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  19. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253–61.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Henan Cancer Hospital, Cancer Hospital Affiliated Zhengzhou University, Zhengzhou University, 127 Dongming Road, Zhengzhou, China

    Ning Li, Wenying Deng, Kang Guo, Wei Shen, Yanping Zhang & Suxia Luo

  2. Department of Pathology, Henan Cancer Hospital, Cancer Hospital Affiliated Zhengzhou University, Zhengzhou University, 127 Dongming Road, Zhengzhou, China

    Jie Ma & Bing Wei

Authors
  1. Ning Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenying Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bing Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yanping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Suxia Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suxia Luo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, N., Deng, W., Ma, J. et al. Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Med Oncol 32, 433 (2015). https://doi.org/10.1007/s12032-014-0433-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0433-6

Keywords

Search

Navigation