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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder

Authors: Jian-Ye Liu, Yong-Hong Li, Huan-Xin Lin, Yi-Ji Liao, Shi-Juan Mai, Zhou-Wei Liu, Zhi-Ling Zhang, Li-Juan Jiang, Jia-Xing Zhang, Hsiang-Fu Kung, Yi-Xin Zeng, Fang-Jian Zhou, Dan Xie

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.

Methods

In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.

Results

Up-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients’ survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis.

Conclusions

Our findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB.
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Literature
1.
Greenlee RT, Hill-Harmon MB, Murray T, Thun M: Cancer statistics, 2001. CA Cancer J Clin. 2001, 51: 15-36. 10.3322/canjclin.51.1.15.CrossRefPubMed
2.
Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, Kiemeney L, Kriegmair M, Montironi R, Murphy WM, Sesterhenn IA, Tachibana M, Weider J: Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 2005, 66: 4-34.CrossRefPubMed
3.
Van Brussel JP, Mickisch GH: Prognostic factors in renal cell and bladder cancer. BJU Int. 1999, 83: 902-908. quiz 908–909CrossRefPubMed
4.
Harvey KF, Pfleger CM, Hariharan IK: The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell. 2003, 114: 457-467. 10.1016/S0092-8674(03)00557-9.CrossRefPubMed
5.
Lai ZC, Wei X, Shimizu T, Ramos E, Rohrbaugh M, Nikolaidis N, Ho LL, Li Y: Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell. 2005, 120: 675-685. 10.1016/j.cell.2004.12.036.CrossRefPubMed
6.
Edgar BA: From cell structure to transcription: Hippo forges a new path. Cell. 2006, 124: 267-273. 10.1016/j.cell.2006.01.005.CrossRefPubMed
7.
Hariharan IK, Bilder D: Regulation of imaginal disc growth by tumor-suppressor genes in Drosophila. Annu Rev Genet. 2006, 40: 335-361. 10.1146/annurev.genet.39.073003.100738.CrossRefPubMed
8.
Harvey K, Tapon N: The Salvador-Warts-Hippo pathway - an emerging tumour-suppressor network. Nat Rev Cancer. 2007, 7: 182-191. 10.1038/nrc2070.CrossRefPubMed
9.
Sudol M: Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene. 1994, 9: 2145-2152.PubMed
10.
Bork P, Sudol M: The WW domain: a signalling site in dystrophin?. Trends Biochem Sci. 1994, 19: 531-533. 10.1016/0968-0004(94)90053-1.CrossRefPubMed
11.
Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, Mu D, Lucito R, Powers S, Lowe SW: Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell. 2006, 125: 1253-1267. 10.1016/j.cell.2006.05.030.CrossRefPubMedPubMedCentral
12.
Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS, Haber DA: Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci USA. 2006, 103: 12405-12410. 10.1073/pnas.0605579103.CrossRefPubMedPubMedCentral
13.
Modena P, Lualdi E, Facchinetti F, Veltman J, Reid JF, Minardi S, Janssen I, Giangaspero F, Forni M, Finocchiaro G, Genitori L, Giordano F, Riccardi R, Schoenmakers EF, Massimino M, Sozzi G: Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J Clin Oncol. 2006, 24: 5223-5233. 10.1200/JCO.2006.06.3701.CrossRefPubMed
14.
Steinhardt AA, Gayyed MF, Klein AP, Dong J, Maitra A, Pan D, Montgomery EA, Anders RA: Expression of Yes-associated protein in common solid tumors. Hum Pathol. 2008, 39: 1582-1589. 10.1016/j.humpath.2008.04.012.CrossRefPubMedPubMedCentral
15.
Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, Lowe SW, Poon RT, Luk JM: Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer. 2009, 115: 4576-4585. 10.1002/cncr.24495.CrossRefPubMedPubMedCentral
16.
Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL: Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007, 21: 2747-2761. 10.1101/gad.1602907.CrossRefPubMedPubMedCentral
17.
Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A, Pan D: Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007, 130: 1120-1133. 10.1016/j.cell.2007.07.019.CrossRefPubMedPubMedCentral
18.
Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, Brummelkamp TR: YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol. 2007, 17: 2054-2060. 10.1016/j.cub.2007.10.039.CrossRefPubMed
19.
Greene FL, Page DL, Fleming ID, April F, Balch CM, Haller DG, Monica M: American Joint Committee on Cancer (AJCC) staging manual. 2002, Philadelphia: Springer, 6CrossRef
20.
Xie D, Sham JS, Zeng WF, Lin HL, Che LH, Wu HX, Wen JM, Fang Y, Hu L, Guan XY: Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray. Int J Cancer. 2003, 107: 896-902. 10.1002/ijc.11514.CrossRefPubMed
21.
Wang Y, Dong Q, Zhang Q, Li Z, Wang E, Qiu X: Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer. Cancer Sci. 2010, 101: 1279-1285. 10.1111/j.1349-7006.2010.01511.x.CrossRefPubMed
22.
Gospodarowicz MK: Staging of bladder cancer. Semin Surg Oncol. 1994, 10: 51-59. 10.1002/ssu.2980100109.CrossRefPubMed
23.
Schrier BP, Hollander MP, van Rhijn BW, Kiemeney LA, Witjes JA: Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy. Eur Urol. 2004, 45: 292-296. 10.1016/j.eururo.2003.10.006.CrossRefPubMed
24.
Hussain SA, James ND: Molecular markers in bladder cancer. Semin Radiat Oncol. 2005, 15: 3-9. 10.1016/j.semradonc.2004.07.007.CrossRefPubMed
25.
Wu S, Liu Y, Zheng Y, Dong J, Pan D: The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. Dev Cell. 2008, 14: 388-398. 10.1016/j.devcel.2008.01.007.CrossRefPubMed
26.
Kang W, Tong JH, Chan AW, Lee TL, Lung RW, Leung PP, So KK, Wu K, Fan D, Yu J, Sung JJ, To KF: Yes-associated protein 1 exhibits oncogenic property in gastric cancer and its nuclear accumulation associates with poor prognosis. Clin Cancer Res. 2011, 17: 2130-2139. 10.1158/1078-0432.CCR-10-2467.CrossRefPubMed
27.
Zhang L, Ye DX, Pan HY, Wei KJ, Wang LZ, Wang XD, Shen GF, Zhang ZY: Yes-associated protein promotes cell proliferation by activating Fos Related Activator-1 in oral squamous cell carcinoma. Oral Oncol. 2011, 47: 693-697. 10.1016/j.oraloncology.2011.06.003.CrossRefPubMed
28.
Ge L, Smail M, Meng W, Shyr Y, Ye F, Fan KH, Li X, Zhou HM, Bhowmick NA: Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis. PLoS One. 2011, 6: e27529-10.1371/journal.pone.0027529.CrossRefPubMedPubMedCentral
29.
Hall CA, Wang R, Miao J, Oliva E, Shen X, Wheeler T, Hilsenbeck SG, Orsulic S, Goode S: Hippo pathway effector Yap is an ovarian cancer oncogene. Cancer Res. 2010, 70: 8517-8525. 10.1158/0008-5472.CAN-10-1242.CrossRefPubMedPubMedCentral
30.
Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S, Sudol M, Shimada Y, Tsuda H, Kawano T, Inazawa J: YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis. 2011, 32: 389-398. 10.1093/carcin/bgq254.CrossRefPubMed
Metadata
Title
Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
Authors
Jian-Ye Liu
Yong-Hong Li
Huan-Xin Lin
Yi-Ji Liao
Shi-Juan Mai
Zhou-Wei Liu
Zhi-Ling Zhang
Li-Juan Jiang
Jia-Xing Zhang
Hsiang-Fu Kung
Yi-Xin Zeng
Fang-Jian Zhou
Dan Xie
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-349

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