YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role
YAP and TAZ Heterogeneity in Primary Liver Cancer: An Analysis of Its Prognostic and Diagnostic Role
复制标题
原发性肝癌雅普和TAZ杂合酶的诊断和预后分析
DOI：
10.3390/ijms20030638
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Roskams, Tania
中科院分区：
文献类型：
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作者：
Van Haele, Matthias;Moya, Ivan M.;Roskams, Tania
原发性肝癌包括一组不同的肝脏肿瘤。这些肿瘤的异质性被视为寻找有效治疗方法的障碍之一。河马途径及其下游转录辅助激活因子YAP和转录辅助激活因子与PDZ结合基序(TAZ)在原发性肝癌的发生发展中起着决定性作用。因此，我们检测了141例肝细胞癌角蛋白19阳性(肝细胞癌K19(+))、肝细胞癌角蛋白19阴性(肝细胞癌K19(-))、肝细胞胆管细胞癌(CHCC-CCA)或胆管细胞癌(CCA)中YAP和TAZ的表达模式。所有CHCC-CCA和CCA患者均有YAP和TAZ的高表达，而仅有部分肝癌患者呈阳性表达。值得注意的是，我们发现这两个标记物的组织核心在CHCC-CCA的挑战性诊断中是有用的。此外，在CHCC-CCA的肝细胞和胆管细胞成分中也观察到YAP和TAZ的阳性表达，提示CHCC-CCA的单一细胞起源。在K19(-)肝细胞癌组中，我们的结果表明，当观察到细胞质时，YAP的表达是一个具有统计学意义的预后不良的预测因子。TAZ的核表达是K19(-)肝细胞癌患者不良无病生存期和总生存期的一个更特异和更独立的预测因子。因此，我们的结果确定了不同水平的YAP/TAZ在各种肝癌中的表达，可用于诊断。
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.