Skip to main content
Top
Published in: Medical Oncology 1/2015

01-01-2015 | Original Paper

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

Authors: Ning Li, Wenying Deng, Jie Ma, Bing Wei, Kang Guo, Wei Shen, Yanping Zhang, Suxia Luo

Published in: Medical Oncology | Issue 1/2015

Login to get access

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.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
7.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference Wang SC. PCNA: a silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci. 2014;35(4):178–86.PubMedCrossRef Wang SC. PCNA: a silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci. 2014;35(4):178–86.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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 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
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedCentralPubMed 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.PubMedCentralPubMed
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference 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 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
Metadata
Title
Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer
Authors
Ning Li
Wenying Deng
Jie Ma
Bing Wei
Kang Guo
Wei Shen
Yanping Zhang
Suxia Luo
Publication date
01-01-2015
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0433-6

Other articles of this Issue 1/2015

Medical Oncology 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.