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Objective: To investigate the correlation between R2(*) value of enhanced T2 star-weighted angiography (ESWAN) sequence and primary hepatocellular carcinoma infiltration and tumor thrombus, and investigate the biological behavior of HCC., Methods: A total of 221 cases of patients' imaging data with MRI examination(including ESWAN sequence) diagnosed as primary HCC were retrospectively analyzed.All the patients were collected from January 2014 to September 2015 in the First Affiliated Hospital of Dalian Medical University.The differences of R2(*) values in different MR types of HCC were analyzed.All patients were divided into infiltration group and non-infiltration group, tumor thrombus group and non-tumor thrombus group, the R2(*) values of the paired groups were compared.The diagnostic efficiency of R2(*) in HCC infiltration and tumor thrombus were evaluated by ROC curve, and to find out the threshold values., Results: The MR types of 221 patients included 90 cases of nodular type, 62 cases of massive type, 69 cases of diffuse type.70 patients had tumor thrombus.The R2(*) values of different MR types were (21.82±8.52), (24.17±8.84)and (34.45±11.73) Hz, respectively.There was no statistically significant difference between the nodular and the massive types (P=0.144), while the difference between the nodular and diffuse type, the massive and diffuse types were statistically significant(P=0.000). The R2(*) values of infiltration group and non-infiltration group were (34.45±11.73) and (22.78±8.70) Hz , the R2(*) values of tumor thrombus group and non-tumor thrombus group were (31.20±12.17) and (24.21±9.90) Hz, the difference also had statistically significant(t=7.397 and 4.534, P=0.000 and 0.000). The AUC of R2(*) values for infiltration and tumor thrombus were 0.804, 0.681. R2(*) ≥24.68 Hz was the threshold value to diagnose the infiltration and tumor thrombus., Conclusion: R2(*) value can be used as a MR non-enhancement quantitative index to evaluate the biological behavior of HCC.

Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC., (© 2011 Macmillan Publishers Limited)

Unlabelled: Hepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof-of-principle studies targeting molecules crucial for the development of HCC. Here, we show that cadherin-17 (CDH17) adhesion molecule is up-regulated in human liver cancers and can transform premalignant liver progenitor cells to produce liver carcinomas in mice. RNA interference-mediated knockdown of CDH17 inhibited proliferation of both primary and highly metastatic HCC cell lines in vitro and in vivo. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt signaling, because growth inhibition and cell death were accompanied by relocalization of beta-catenin to the cytoplasm and a concomitant reduction in cyclin D1 and an increase in retinoblastoma., Conclusion: Our results identify CDH17 as a novel oncogene in HCC and suggest that CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy.

Background: Yes-associated protein (YAP), a downstream target of the Hippo signaling pathway, was recently linked to hepatocarcinogenesis in a mouse hepatocellular carcinoma (HCC) model. The objective of the current study was to investigate the clinical significance of YAP in HCC and its prognostic values in predicting survival and tumor recurrence., Methods: The authors collected 177 pairs of tumor and adjacent nontumor tissue from HCC patients with definitive clinicopathologic and follow-up data. YAP expression was determined by immunohistochemistry, Western blot analysis, and quantitative polymerase chain reaction. Association of YAP with each clinicopathologic feature was analyzed by Pearson chi-square test, and HCC-specific disease-free survival and overall survival by Kaplan-Meier curves and log-rank test. Multivariate Cox regression analyses of YAP in HCC were also performed., Results: YAP was expressed in the majority of HCC cases (approximately 62%) and mainly accumulated in the tumor nucleus. Overexpression of YAP in HCC was significantly associated with poorer tumor differentiation (Edmonson grade; P = .021) and high serum alpha-fetoprotein (AFP) level (P < .001). Kaplan-Meier and Cox regression data indicated that YAP was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.653; 95% confidence interval [95% CI], 1.081-2.528 [P = .02]) and overall survival (HR, 2.148; 95% CI, 1.255-3.677 [P = .005])., Conclusions: YAP is an independent prognostic marker for overall survival and disease-free survival times of HCC patients and clinicopathologically associated with tumor differentiation and serum AFP level. It is a potential therapeutic target for this aggressive malignancy., (2009 American Cancer Society.)

To identify potential oncofetal biomarkers that distinguish hepatocellular carcinoma (HCC) from healthy liver tissues, we compared and analyzed the proteomic profiles of mouse livers at different developmental stages. Fetal (E13.5, E16.5), newborn (NB), postnatal (3-week) and adult (3-month) livers were isolated and profiled by 2-D PAGE. Statistical analysis using linear regression and false discovery rate (FDR) revealed that 361 protein spots showed significant changes. Unsupervised hierarchical tree analysis segregated the proteins into fetal, NB, and postnatal-adult clusters. Distinctive protein markers were identified by MALDI-TOF/MS and the corresponding mRNA profiles were further determined by Q-PCR. Fetal markers (hPCNA, hHSP7C, hHEM6) and postnatal-adult markers (hARGI1, hASSY, hBHMT, hFABPL) were selected for testing against a panel of seven human hepatocyte/HCC cell lines and 59 clinical specimens. The fetal proteins were found to be overexpressed in the metastatic HCC cell lines and the tumor tissues, whereas the postnatal-adult proteins were expressed in non-tumor tissues and normal hepatocytes. This "Ying-Yang" pattern, as orchestrated by distinct fetal and adult markers, is hypothesized to indicate the progressive change of the liver from a growing, less-differentiated organ into a functional metabolic center. Thus, embryogenesis and tumorigenesis share certain oncofetal markers and adult "hepatic" phenotypes are lost in HCC.