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Tumor Biology
Published in: Tumor Biology 2/2015

01-02-2015 | Research Article

Cripto-1 expression and its prognostic value in human bladder cancer patients

Authors: Bingbing Wei, Wei Jin, Jun Ruan, Zhuoqun Xu, You Zhou, Jiabei Liang, Huan Cheng, Ke Jin, Xing Huang, Peng Lu, Qiang Hu

Published in: Tumor Biology | Issue 2/2015

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Abstract

Cripto-1 is an important embryonic gene that involved in self-renewal and maintenance of pluripotency of stem cells. Overexpression of Cripto-1 has been found to be correlated with tumorigenesis and may affect tumor recurrence and metastasis. The previous studies indicate that Cripto-1 might be a potential prognostic biomarker for several malignancies. The aim of this study is to examine Cripto-1 expression pattern and clinicopathological significance in human bladder cancer patients. We investigated Cripto-1 expression in 30 paired bladder cancer tissues and corresponding noncancerous bladder tissues using real-time quantitative RT-PCR (qRT-PCR). Moreover, Cripto-1 expression in 130 bladder cancer specimens and bladder cancer T24 and 5637 cells were analyzed using immunohistochemistry and immunofluorescence assays. The recurrence/metastasis-free survival was assessed by Kaplan–Meier method and log-rank test. Cox regression was also used for univariate and multivariate analyses of prognostic factors. The results showed that Cripto-1 expression is increased in bladder cancer tissues and is significantly associated with tumor size (P = 0.005) and tumor grade (P = 0.035). In addition, the expression level of Cripto-1 in bladder cancer was also found to be significantly associated with SRY-related HMG-box gene 2 expression (P = 0.003) and Ki-67 (P = 0.001). Compared with the patients with low Cripto-1 expression, the patients with high Cripto-1 expression had significantly poorer recurrence/metastasis-free survival (P = 0.011). Cox regression showed that Cripto-1 might be an independent prognostic factor for recurrence/metastasis-free survival (P = 0.036). Our findings suggest that high Cripto-1 expression might be involved in the development of bladder cancer and a potentially effective prognostic marker in bladder cancer patients.
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
2.
3.
Dinney CP, McConkey DJ, Millikan RE, Wu X, Bar-Eli M, Adam L, et al. Focus on bladder cancer. Cancer Cell. 2004;6:111–6.CrossRefPubMed
4.
5.
Li Y, Izumi K, Miyamoto H. The role of the androgen receptor in the development and progression of bladder cancer. Jpn J Clin Oncol. 2012;42:569–77.CrossRefPubMed
6.
7.
8.
Nishida S, Hirohashi Y, Torigoe T, Inoue R, Kitamura H, Tanaka T, et al. Prostate cancer stem-like cells/cancer-initiating cells have an autocrine system of hepatocyte growth factor. Cancer Sci. 2013;104:431–6.CrossRefPubMed
9.
Wang S, Xu ZY, Wang LF, Su W. CD133+ cancer stem cells in lung cancer. Front Biosci. 2013;18:447–53.CrossRef
10.
Hepburn AC, Veeratterapillay R, Williamson SC, El-Sherif A, Sahay N, Thomas HD, et al. Side population in human non-muscle invasive bladder cancer enriches for cancer stem cells that are maintained by MAPK signalling. PLoS One. 2012;7:e50690.CrossRefPubMedPubMedCentral
11.
Falso MJ, Buchholz BA, White RW. Stem-like cells in bladder cancer cell lines with differential sensitivity to cisplatin. Anticancer Res. 2012;32:733–8.PubMed
12.
Zhang Y, Wang Z, Yu J, Shi J, Wang C, Fu W, et al. Cancer stem-like cells contribute to cisplatin resistance and progression in bladder cancer. Cancer Lett. 2012;322:70–7.CrossRefPubMed
13.
Bianco C, Castro NP, Baraty C, Rollman K, Held N, Rangel MC, et al. Regulation of human Cripto-1 expression by nuclear receptors and DNA promoter methylation in human embryonal and breast cancer cells. J Cell Physiol. 2013;228:1174–88.CrossRefPubMedPubMedCentral
14.
Dono R, Montuori N, Rocchi M, De Ponti-Zilli L, Ciccodicola A, Persico MG. Isolation and characterization of the CRIPTO autosomal gene and its X-linked related sequence. Am J Hum Genet. 1991;49:555–65.PubMedPubMedCentral
15.
Nagaoka T, Karasawa H, Turbyville T, Rangel MC, Castro NP, Gonzales M, et al. Cripto-1 enhances the canonical Wnt/beta-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors. Cell Signal. 2013;25:178–89.CrossRefPubMed
16.
Bianco C, Normanno N, Salomon DS, Ciardiello F. Role of the cripto (EGF-CFC) family in embryogenesis and cancer. Growth Factors. 2004;22:133–9.CrossRefPubMed
17.
Strizzi L, Bianco C, Normanno N, Salomon D. Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis. Oncogene. 2005;24:5731–41.CrossRefPubMed
18.
Yoon HJ, Hong JS, Shin WJ, Lee YJ, Hong KO, Lee JI, et al. The role of Cripto-1 in the tumorigenesis and progression of oral squamous cell carcinoma. Oral Oncol. 2011;47:1023–31.CrossRefPubMed
19.
de Castro NP, Rangel MC, Nagaoka T, Salomon DS, Bianco C. Cripto-1: an embryonic gene that promotes tumorigenesis. Future Oncol. 2010;6:1127–42.CrossRefPubMed
20.
Rangel MC, Karasawa H, Castro NP, Nagaoka T, Salomon DS, Bianco C. Role of Cripto-1 during epithelial-to-mesenchymal transition in development and cancer. Am J Pathol. 2012;180:2188–200.CrossRefPubMedPubMedCentral
21.
Bianco C, Rangel MC, Castro NP, Nagaoka T, Rollman K, Gonzales M, et al. Role of Cripto-1 in stem cell maintenance and malignant progression. Am J Pathol. 2010;177:532–40.CrossRefPubMedPubMedCentral
22.
23.
Jia X, Li X, Xu Y, Zhang S, Mou W, Liu Y, et al. SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell. J Mol Cell Biol. 2011;3:230–8.CrossRefPubMed
24.
Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 2012;31:1354–65.CrossRefPubMed
25.
Annovazzi L, Mellai M, Caldera V, Valente G, Schiffer D. SOX2 expression and amplification in gliomas and glioma cell lines. Cancer Genomics Proteomics. 2011;8:139–47.PubMed
26.
27.
Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Muller F, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 2011;11:42.CrossRefPubMedPubMedCentral
28.
Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembele D, et al. SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One. 2010;5:e8960.CrossRefPubMedPubMedCentral
29.
Xiang R, Liao D, Cheng T, Zhou H, Shi Q, Chuang TS, et al. Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer. Br J Cancer. 2011;104:1410–7.CrossRefPubMedPubMedCentral
30.
Rodriguez-Alonso A, Pita-Fernandez S, Gonzalez-Carrero J, Nogueira-March JL. p53 and ki67 expression as prognostic factors for cancer-related survival in stage T1 transitional cell bladder carcinoma. Eur Urol. 2002;41:182–8. discussion 8–9.CrossRefPubMed
31.
Oderda M, Ricceri F, Pisano F, Fiorito C, Gurioli A, Casetta G, et al. Prognostic factors including Ki-67 and p53 in Bacillus Calmette-Guerin-treated non-muscle-invasive bladder cancer: a prospective study. Urol Int. 2013;90:184–90.CrossRefPubMed
32.
Cattoretti G, Becker MH, Key G, Duchrow M, Schluter C, Galle J, et al. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992;168:357–63.CrossRefPubMed
33.
Bertz S, Otto W, Denzinger S, Wieland WF, Burger M, Stohr R, et al. Combination of CK20 and Ki-67 Immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer. Eur Urol. 2014;65:218–26.CrossRefPubMed
34.
Acikalin D, Oner U, Can C, Acikalin MF, Colak E. Predictive value of maspin and Ki-67 expression in transurethral resection specimens in patients with T1 bladder cancer. Tumori. 2012;98:344–50.PubMed
35.
Shen Y, Guo X, Wang Y, Qiu W, Chang Y, Zhang A, et al. Expression and significance of histone H3K27 demethylases in renal cell carcinoma. BMC Cancer. 2012;12:470.CrossRefPubMedPubMedCentral
36.
Ge N, Lin HX, Xiao XS, Guo L, Xu HM, Wang X, et al. Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma. J Transl Med. 2010;8:94.CrossRefPubMedPubMedCentral
37.
Ruan J, Wei B, Xu Z, Yang S, Zhou Y, Yu M, et al. Predictive value of Sox2 expression in transurethral resection specimens in patients with T1 bladder cancer. Med Oncol. 2013;30:445.CrossRefPubMed
38.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.CrossRefPubMed
39.
Verga Falzacappa MV, Ronchini C, Reavie LB, Pelicci PG. Regulation of self-renewal in normal and cancer stem cells. FEBS J. 2012;279:3559–72.CrossRefPubMed
40.
Zeimet AG, Reimer D, Sopper S, Boesch M, Martowicz A, Roessler J, et al. Ovarian cancer stem cells. Neoplasma. 2012;59:747–55.CrossRefPubMed
41.
Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140:62–73.CrossRefPubMed
42.
Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell. 2010;141:583–94.CrossRefPubMedPubMedCentral
43.
Dembinski JL, Krauss S. Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis. 2009;26:611–23.CrossRefPubMedPubMedCentral
44.
Haraguchi N, Ishii H, Mimori K, Tanaka F, Ohkuma M, Kim HM, et al. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest. 2010;120:3326–39.CrossRefPubMedPubMedCentral
45.
Strizzi L, Abbott DE, Salomon DS, Hendrix MJ. Potential for cripto-1 in defining stem cell-like characteristics in human malignant melanoma. Cell Cycle. 2008;7:1931–5.CrossRefPubMedPubMedCentral
46.
Byrne RL, Autzen P, Birch P, Robinson MC, Gullick WJ, Neal DE, et al. The immunohistochemical detection of cripto-1 in benign and malignant human bladder. J Pathol. 1998;185:108–11.CrossRefPubMed
47.
Hong SP, Lee EK, Park JY, Jeon TJ, Bang S, Park S, et al. Cripto-1 overexpression is involved in the tumorigenesis of gastric-type and pancreatobiliary-type intraductal papillary mucinous neoplasms of the pancreas. Oncol Rep. 2009;21:19–24.PubMed
48.
Wechselberger C, Strizzi L, Kenney N, Hirota M, Sun Y, Ebert A, et al. Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma. Oncogene. 2005;24:4094–105.CrossRefPubMed
49.
Zhong XY, Zhang LH, Jia SQ, Shi T, Niu ZJ, Du H, et al. Positive association of up-regulated Cripto-1 and down-regulated E-cadherin with tumour progression and poor prognosis in gastric cancer. Histopathology. 2008;52:560–8.CrossRefPubMed
50.
Metadata
Title
Cripto-1 expression and its prognostic value in human bladder cancer patients
Authors
Bingbing Wei
Wei Jin
Jun Ruan
Zhuoqun Xu
You Zhou
Jiabei Liang
Huan Cheng
Ke Jin
Xing Huang
Peng Lu
Qiang Hu
Publication date
01-02-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2695-1

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