Wnt signaling and hepatocarcinogenesis: The hepatoblastoma model

Byun²,

2011

BMB Reports

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are biochemical markers used to test for liver diseases. Copy number variation (CNV) plays an important role in determining complex traits and is an emerging area in the study various diseases. We performed a genome-wide association study with liver function biomarkers AST and ALT in 407 unrelated Koreans. We assayed the genome-wide variations on an Affymetrix Genome-Wide 6.0 array, and CNVs were analyzed using HelixTree. Using single linear regression, 32 and 42 CNVs showed significance for AST and ALT, respectively (P value ＜ 0.05). We compared CNV-based genes between the current study (KARE2; AST-140, ALT-172) and KARE1 (AST-1885, ALT-773) using NetBox. Results showed 9 genes (CIDEB, DFFA, PSMA3, PSMC5, PSMC6, PSMD12, PSMF1, SDC4, and SIAH1) were overlapped for AST, but no overlapped genes were found for ALT. Functional gene annotation analysis shown the proteasome pathway, Wnt signaling pathway, programmed cell death, and protein binding. [BMB reports 2011; 44(9): 578-583]

Section: Discussionmentioning

confidence: 99%

A replication study of genome-wide CNV association for hepatic biomarkers identifies nine genes associated with liver function

Byun²,

2011

BMB Reports

“…CTNNB1 mutations are found in ≈70% of HB. Accordingly, HB stands at the first rank among human cancers endowed with constitutive activation of the Wnt signaling pathway [19]. Wnt signaling pathway regulates progenitor cell expansion and embryonic lineage decisions and its disruption has been linked to developmental defects and cancer [20].…”

Section: Editorialmentioning

confidence: 99%

Hepatoblastoma Etiopathogenesis

RIR¹,

Armengol²,

JJG³

2016

J Carcinog Mutagene

EditorialHepatoblastoma (HB) is the predominant form of pediatric liver cancer, usually arising in young children under 3 years of age [1], but it is a rare pediatric cancer with a very low worldwide incidence (<2 cases per million children under 18 years) [2]. Hepatocellular carcinoma (HCC) can also be diagnosed in children but with much lower incidence, usually found in the teenage population in association with predisposing conditions, such as the presence of underlying liver diseases (i.e., tyrosinemia and several cholestatic syndromes). As compared with HB, the prognostic of HCC is often poorer. A third type of primary liver cancer that appears at the late childhood and adolescence was initially called transitional liver cell tumor (TLCT), because it has a mixture of histological patterns characteristic of HB and HCC [3]. This cancer has been recently classified in a new provisional category named hepatocellular neoplasm not otherwise specified [4], awaiting for a better characterization, in an international symposium aiming to develop a consensus classification system for pediatric liver malignancies.Overall survival of patients with HB has notably improved from 30% in the 1970s to 70-80% nowadays thanks to the incorporation to the treatment of adjuvant and neoadjuvant chemotherapy using cisplatin and doxorubicin combined with efficient surgical approaches, including liver transplantation [5]. However, there are very limited treatment options for patients suffering from immature, invasive, and metastatic HB resistant to conventional first-line chemotherapeutic protocols, being the survival of these patients usually less than 3 years. The International Childhood Liver Tumor Strategy Group (SIOPEL) defined a prognostic stratification system of HB patients taking into consideration PRETEXT stage, metastatic disease, serum α-fetoprotein levels, multifocality, age and histology characterized by small undifferentiated cells [6]. Importantly, a recent study of the Children's Hepatic tumors International Collaboration (CHIC) group has confirmed these prognostic risk factors and identified new ones through a large-scale analysis using an extensive database including 1605 HB cases [7]. Patient stratification and treatment taking into account molecular biomarkers are the future challenges facing clinicians. High-throughput molecular studies of aggressive tumors highly refractory to anticancer drugs have the unique potential to provide a rational basis and new tools (biomarkers/molecular targets) for improving patient stratification and defining more specific and molecular-based therapies.Because HB is a rare tumor, most of the few existing studies have been carried out in small groups of patients, and this fact, together with the existence of several histologic subtypes without a clear consensus for their classification, has hindered advances in the characterization of different aspects of this liver cancer. Histologically, HB is usually composed of combinations of epithelial, mesenchymal, undifferentiated and other ...

International Journal of Oncology

“…HCC has a poor prognosis and present treatments are surgical resection, transplantation and chemotherapy (101). The Wnt signaling pathway plays an important role in hepatocellular development, and increasing evidence shows that the Wnt signaling pathway is also involved in liver tumorigenesis (102). A recent report showed that the Wnt signaling pathway has been observed to be activated in at least 1/3 of HCC (103).…”

Section: Wnt/β-catenin Signaling Pathwaymentioning

confidence: 99%

Notch and Wnt signaling pathway in cancer: Crucial role and potential therapeutic targets (Review)

Xiao

Xin

Tang

et al. 2015

Abstract. There is no radical cure for all cancer types. The most frequently used therapies are surgical treatment, radiotherapy and chemotherapy. However, recrudescence, radiation resistance and chemotherapy resistance are the most challenging issues in clinical practice. To address these issues, they should be further studied at the molecular level, and the signaling pathways involved represent a promising avenue for this research. In the present review, we mainly discuss the components and mechanisms of activation of the Notch and Wnt signaling pathways, and we summarize the recent research efforts on these two pathways in different cancers.