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Open AccessArticle

YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role

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Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium
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Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Americas, Quito 170503, Ecuador
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VIB Center for Cancer Biology, and KU Leuven Department of Oncology, University of Leuven, 3000 Leuven, Belgium
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Motor Control Laboratory, Movement Control and Neuroplasticity Research Group, Department of Kinesiology, KU Leuven, 3000 Leuven, Belgium
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Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne 3000, UK
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Department of Hepatology, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium
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Department of Abdominal Surgery, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium
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Abdominal Transplantation Surgery, KU Leuven and University Hospitals Leuven, 3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 638; https://doi.org/10.3390/ijms20030638
Received: 28 December 2018 / Revised: 25 January 2019 / Accepted: 29 January 2019 / Published: 1 February 2019
Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19+), hepatocellular carcinoma keratin 19 negative (HCC K19), combined hepatocellular–cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA). All cHCC-CCA and CCA patients showed high expression levels for YAP and TAZ, while only some patients of the HCC group were positive. Notably, we found that a histoscore of both markers is useful in the challenging diagnosis of cHCC-CCA. In addition, positivity for YAP and TAZ was observed in the hepatocellular and cholangiocellular components of cHCC-CCA, which suggests a single cell origin in cHCC-CCA. Within the K19 HCC group, our results demonstrate that the expression of YAP is a statistically significant predictor of poor prognosis when observed in the cytoplasm. Nuclear expression of TAZ is an even more specific and independent predictor of poor disease-free survival and overall survival of K19 HCC patients. Our results thus identify different levels of YAP/TAZ expression in various liver cancers that can be used for diagnostics. View Full-Text
Keywords: HCC; cHCC-CCA; CCA; YAP; TAZ; Keratin 19; Hepatic progenitor cells HCC; cHCC-CCA; CCA; YAP; TAZ; Keratin 19; Hepatic progenitor cells
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Van Haele, M.; Moya, I.M.; Karaman, R.; Rens, G.; Snoeck, J.; Govaere, O.; Nevens, F.; Verslype, C.; Topal, B.; Monbaliu, D.; Halder, G.; Roskams, T. YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role. Int. J. Mol. Sci. 2019, 20, 638.

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