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

Lookup NU author(s): Dr Olivier Govaere

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Van Haele M, Moya IM, Karaman R, Rens G, Snoeck J, Govaere O, Nevens F, Verslype C, Topal B, Monbaliu D, Halder G, Roskams T

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2019

Volume: 20

Issue: 3

Online publication date: 01/02/2019

Acceptance date: 29/01/2019

ISSN (electronic): 1422-0067

Publisher: MDPIAG

URL: https://doi.org/10.3390/ijms20030638

DOI: 10.3390/ijms20030638

PubMed id: 30717258


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