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- Title
YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role.
- Authors
Van Haele, Matthias; Moya, Iván M.; Karaman, Ruçhan; Rens, Guy; Snoeck, Janne; Govaere, Olivier; Nevens, Frederik; Verslype, Chris; Topal, Baki; Monbaliu, Diethard; Halder, Georg; Roskams, Tania
- 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.
- Subjects
LIVER cancer; CARCINOGENESIS; CHOLANGIOCARCINOMA; PROGNOSIS; KERATIN
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 3, p638
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20030638