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Article

Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma

  • Authors:
    • Xiangguo Tian
    • Zhixin Cao
    • Qian Ding
    • Zhen Li
    • Chunqing Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
  • Pages: 2059-2065
    |
    Published online on: June 24, 2019
       https://doi.org/10.3892/ol.2019.10522
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Abstract

The aim of the present study was to investigate the expression of epithelial mesenchymal transition (EMT)‑associated proteins and their prognostic value in intrahepatic cholangiocarcinoma (ICC). The expression of six EMT‑associated proteins, including E‑cadherin, N‑cadherin, Vimentin, Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug) and S100 calcium binding protein A4 (S100A4) was determined by immunohistochemistry in 109 patients with ICC who had received surgery. Survival analysis showed that patients with low E‑cadherin expression (P<0.001) or high S100A4 (P<0.001) or Snail (P<0.001) expression had a reduced survival time. Based on the numbers of alterations in the expression of EMT‑associated proteins as determined by immunohistochemical analysis, the patients were categorized as low (score, 0‑3; n=75) or high (score, ≥4; n=34) EMT expression groups. The high EMT expression group was significantly associated with positive lymph node metastasis (P=0.023) and late Tumor‑Node‑Metastasis (TNM) stage (P<0.001). Furthermore, patients in the high EMT expression group had a significantly poorer overall survival time than those in the low EMT expression group (P<0.001). Multivariate analysis indicated that EMT status was a significant independent predictor for overall survival time (P=0.004), and was linked to surgical margin (P=0.013) and TNM stage (P<0.001). In conclusion, the reduced expression of E‑cadherin and high expression of Snail and S100A4 were significantly associated with the poor survival of patients with ICC after surgery. The EMT protein expression status was associated with ICC progression, and may be considered as an independent prognostic indicator for patients with ICC.
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1 

Razumilava N and Gores GJ: Cholangiocarcinoma. Lancet. 383:2168–2179. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM and Gores GJ: Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 60:1268–1289. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Gupta A and Dixon E: Epidemiology and risk factors: Intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr. 6:101–104. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Zhang H, Shen F, Han J, Shen YN, Xie GQ, Wu MC and Yang T: Epidemiology and surgical management of intrahepatic cholangiocarcinoma. Hepat Oncol. 3:83–91. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Shaib YH, Davila JA, McGlynn K and El-Serag HB: Rising incidence of intrahepatic cholangiocarcinoma in the United States: A true increase? J Hepatol. 40:472–477. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Baba H and Mori M: Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 101:293–299. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial- mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Zeisberg M and Neilson EG: Biomarkers for epithelial-mesenchymal transitions. J Clin Invest. 119:1429–1437. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Tania M, Khan MA and Fu J: Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer. Tumour Biol. 35:7335–7342. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Wen J, Luo KJ, Liu QW, Wang G, Zhang MF, Xie XY, Yang H, Fu JH and Hu Y: The epithelial-mesenchymal transition phenotype of metastatic lymph nodes impacts the prognosis of esophageal squamous cell carcinoma patients. Oncotarget. 7:37581–37588. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Kim MA, Lee HS, Lee HE, Kim JH, Yang HK and Kim WH: Prognostic importance of epithelial-mesenchymal transition- related protein expression in gastric carcinoma. Histopathology. 54:442–451. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Cao H, Xu E, Liu H, Wan L and Lai M: Epithelial-mesenchymal transition in colorectal cancer metastasis: A system review. Pathol Res Pract. 211:557–569. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Giannelli G, Koudelkova P, Dituri F and Mikulits W: Role of epithelial to mesenchymal transition in hepatocellular carcinoma. J Hepatol. 65:798–808. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Vaquero J, Guedj N, Clapéron A, Nguyen Ho-Bouldoires TH, Paradis V and Fouassier L: Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks. J Hepatol. 66:424–441. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Huang XY, Zhang C, Cai JB, Shi GM, Ke AW, Dong ZR, Zhang PF, Fan J, Peng BG and Zhou J: Comprehensive multiple molecular profile of epithelial mesenchymal transition in intrahepatic cholangiocarcinoma patients. PLoS One. 9:e968602014. View Article : Google Scholar : PubMed/NCBI

17 

Nitta T, Mitsuhashi T, Hatanaka Y, Miyamoto M, Oba K, Tsuchikawa T, Suzuki Y, Hatanaka KC, Hirano S and Matsuno Y: Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: Comprehensive immunohistochemical study using a tissue microarray. Br J Cancer. 111:1363–1372. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Yao X, Wang X, Wang Z, Dai L, Zhang G, Yan Q and Zhou W: Clinicopathological and prognostic significance of epithelial mesenchymal transition-related protein expression in intrahepatic cholangiocarcinoma. Onco Targets Ther. 5:255–261. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Ryu HS, Chung JH, Lee K, Shin E, Jing J, Choe G, Kim H, Xu X, Lee HE, Kim DG, et al: Overexpression of epithelial-mesenchymal transition-related markers according to cell dedifferentiation: Clinical implications as an independent predictor of poor prognosis in cholangiocarcinoma. Hum Pathol. 43:2360–2370. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Sobin LH, Gospodarowicz MK and Wittekind CH: TNM Classification of Malignant Tumours. 7th edition. Wiley-Blackwell; Oxford: pp. 122–128. 2009

21 

Tian XG, Wang QZ, Li Y, Hu JH, Wu L, Ding Q and Zhang C: The expression of S100A4 protein in human intrahepatic cholangiocarcinoma: Clinicopathologic significance and prognostic value. Pathol Oncol Res. 21:195–201. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Shiozaki H, Tahara H, Oka H, Miyata M, Kobayashi K, Tamura S, Iihara K, Doki Y, Hirano S, Takeichi M, et al: Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 139:17–23. 1991.PubMed/NCBI

23 

Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED and Thompson EW: Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 213:374–383. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Mazzucchelli L: Protein S100A4: Too long overlooked by pathologists? Am J Pathol. 160:7–13. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Boye K and Maelandsmo GM: S100A4 and metastasis: A small actor playing many roles. Am J Pathol. 176:528–535. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Fabris L, Cadamuro M, Moserle L, Dziura J, Cong X, Sambado L, Nardo G, Sonzogni A, Colledan M, Furlanetto A, et al: Nuclear expression of S100A4 calcium-binding protein increases cholangiocarcinoma invasiveness and metastasization. Hepatology. 54:890–899. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Mikami S, Katsube K, Oya M, Ishida M, Kosaka T, Mizuno R, Mukai M and Okada Y: Expression of Snail and Slug in renal cell carcinoma: E-cadherin repressor Snail is associated with cancer invasion and prognosis. Lab Invest. 91:1443–1458. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Kurrey NK, K A and Bapat SA: Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level. Gynecol Oncol. 97:155–165. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Emadi Baygi M, Soheili ZS, Schmitz I, Sameie S and Schulz WA: Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines. Cell Biol Toxicol. 26:553–567. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Blechschmidt K, Sassen S, Schmalfeldt B, Schuster T, Höfler H and Becker KF: The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br J Cancer. 98:489–495. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Kong D, Liang J, Li R, Liu S, Wang J, Zhang K and Chen D: Prognostic significance of snail expression in hilar cholangiocarcinoma. Braz J Med Biol Res. 45:617–624. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Poser I, Dominguez D, de Herreros AG, Varnai A, Buettner R and Bosserhoff AK: Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J Biol Chem. 276:24661–24666. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F and Nieto MA: The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2:76–83. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Zhang KJ, Wang DS, Zhang SY, Jiao XL, Li CW, Wang XS, Yu QC and Cui HN: The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma. J Exp Clin Cancer Res. 29:882010. View Article : Google Scholar : PubMed/NCBI

36 

Zhang KJ, Zhang BY, Zhang KP, Tang LM, Liu SS, Zhu DM and Zhang DL: Clinicopathologic significance of slug expression in human intrahepatic cholangiocarcinoma. World J Gastroenterol. 16:2554–2557. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tian X, Cao Z, Ding Q, Li Z and Zhang C: Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma. Oncol Lett 18: 2059-2065, 2019.
APA
Tian, X., Cao, Z., Ding, Q., Li, Z., & Zhang, C. (2019). Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma. Oncology Letters, 18, 2059-2065. https://doi.org/10.3892/ol.2019.10522
MLA
Tian, X., Cao, Z., Ding, Q., Li, Z., Zhang, C."Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma". Oncology Letters 18.2 (2019): 2059-2065.
Chicago
Tian, X., Cao, Z., Ding, Q., Li, Z., Zhang, C."Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma". Oncology Letters 18, no. 2 (2019): 2059-2065. https://doi.org/10.3892/ol.2019.10522
Copy and paste a formatted citation
x
Spandidos Publications style
Tian X, Cao Z, Ding Q, Li Z and Zhang C: Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma. Oncol Lett 18: 2059-2065, 2019.
APA
Tian, X., Cao, Z., Ding, Q., Li, Z., & Zhang, C. (2019). Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma. Oncology Letters, 18, 2059-2065. https://doi.org/10.3892/ol.2019.10522
MLA
Tian, X., Cao, Z., Ding, Q., Li, Z., Zhang, C."Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma". Oncology Letters 18.2 (2019): 2059-2065.
Chicago
Tian, X., Cao, Z., Ding, Q., Li, Z., Zhang, C."Prognostic value of multiple epithelial mesenchymal transition‑associated proteins in intrahepatic cholangiocarcinoma". Oncology Letters 18, no. 2 (2019): 2059-2065. https://doi.org/10.3892/ol.2019.10522
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