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Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma.

ABSTRACT: Combined hepatocellular-cholangiocarcinoma (cHC-CC) and some hepatocellular carcinomas (HCCs) express stemness-related markers, such as epithelial adhesion molecule (EpCAM) and keratin 19 (K19), the expression of which has been reported to be associated with more aggressive behavior therein than in HCCs without. Yes-associated protein 1 (YAP1), a potential oncogene, is known to promote stem cell proliferation. In the present study, YAP1 expression and clinicopathological features were evaluated and compared among three groups comprising 36 HCCs that expressed both EpCAM and K19, 64 HCCs that did not express EpCAM and K19, and 58 cHC-CCs, which consisted of 38 cases of the classical type and 20 cases of the intermediate-cell subtype. YAP1 expression was more frequently noted in EpCAM(+)/K19(+) HCCs (55.6%) and in cHC-CCs (67.2%) than in EpCAM(-)/K19(-) HCCs (17.2%) (P<0.001 for both). In cHC-CCs, YAP1 expression was observed in 63% of classical type cHC-CCs and in 75% of the intermediate subtype; moreover, such expression was correlated with poorer histological differentiation (P?=?0.017) and was more frequently noted in transition zones than in HCC areas (P?=?0.060). Disease-free and overall survival showed a statistically significant difference among the three groups: disease-free survival was highest for EpCAM(-)/K19(-) HCCs and lowest for cHC-CCs, with EpCAM(+)/K19(+) HCCs falling in between (P<0.05). Overall survival rate was lower in HCCs and cHC-CCs with YAP1 expression compared to those without (P?=?0.05), whereas disease-free survival showed no significant difference according to YAP1 expression. Increased YAP1 expression was more frequently found in cHC-CCs and HCCs with stemness than in HCCs without, and a YAP1 pathway is suggested to be involved in the obtainment stemness characteristics in HCCs and cHC-CCs.

SUBMITTER: Kim GJ

PROVIDER: S-EPMC3782432 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma.

Kim Gi Jeong GJ Kim Hyunki H Park Young Nyun YN

PloS one 20130924 9

Combined hepatocellular-cholangiocarcinoma (cHC-CC) and some hepatocellular carcinomas (HCCs) express stemness-related markers, such as epithelial adhesion molecule (EpCAM) and keratin 19 (K19), the expression of which has been reported to be associated with more aggressive behavior therein than in HCCs without. Yes-associated protein 1 (YAP1), a potential oncogene, is known to promote stem cell proliferation. In the present study, YAP1 expression and clinicopathological features were evaluated ...[more]

PMID: 24086533

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Project description:BackgroundEvidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generating CSCs. In the present study, we investigate whether oxaliplatin-treated cancer tissues possess characteristics of CSCs, and explore oxaliplatin resistance in these tissues.MethodsHepatocellular carcinoma cells (MHCC97H cells) were subcutaneously injected into mice to form tumors, and the mice were intravenously treated with either oxaliplatin or glucose. Five weeks later, the tumors were orthotopically xenografted into livers of other mice, and these mice were treated with either oxaliplatin or glucose. Metastatic potential, sensitivity to oxaliplatin, and expression of CSC-related markers in the xenografted tumor tissues were evaluated. DNA microarrays were used to measure changes in gene expression as a result of oxaliplatin treatment. Additionally, an oxaliplatin-resistant cell line (MHCC97H-OXA) was established to assess insulin-like growth factor 1 secretion, cell invasion, cell colony formation, oxaliplatin sensitivity, and expression of CSC-related markers. The effects of an insulin-like growth factor 1 receptor inhibitor were also assessed.ResultsOxaliplatin treatment inhibited subcutaneous tumor growth. Tumors from oxaliplatin-treated mice that were subsequently xenografted into livers of other mice exhibited that decreasing sensitivity to oxaliplatin and increasing pulmonary metastatic potential. Among the expression of CSC-related proteins, the gene for insulin-like growth factor 1, was up-regulated expecially in these tumor tissues. Additionally, MHCC97H-OXA cells demonstrated that increasing cell invasion, colony formation, and expression of insulin-like growth factor 1 and CSC-related markers, whereas treatment with an inhibitor of the insulin-like growth factor 1 receptor suppressed these effects.ConclusionMaintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1.

Dataset Information

Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma.

Publications

Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma.

Similar Datasets

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