Sortilin-Driven Cancer Secretome Enhances Tumorigenic Properties of Hepatocellular Carcinoma via de Novo Lipogenesis.

A growing body of evidence suggests de novo lipogenesis as a key metabolic pathway adopted by cancers to fuel tumorigenic processes. While increased de novo lipogenesis has also been reported in hepatocellular carcinoma (HCC), understanding on molecular mechanisms driving de novo lipogenesis remains limited. In the present study, the functional role of sortilin, a member of the vacuolar protein sorting 10 protein receptor family, in HCC was investigated.

Sex-specific analysis of microRNA profiles in HBV-associated cirrhosis by small RNA-sequencing.

Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex-specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)-associated cirrhosis by small RNA-sequencing using clinical tissue samples.

Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma.

Background & Aims: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs.

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV-associated liver fibrosis.

Stanniocalcin 1 (STC1), a secreted protein, is upregulated in human cancers including hepatocellular carcinoma (HCC). While most HCCs develop from chronic liver disease, which involves progressive parenchymal injury and fibrosis, the role of STC1 in this preneoplastic stage remains poorly understood. In this study we investigated the clinical relevance and functional significance of secreted STC1 in liver fibrosis.

An Immunohistochemical Study of β-catenin Expression and Immune Cell Population in Metastatic Carcinoma to the Liver.

The liver is the commonest site of cancer metastasis. In this study, we asked whether the immune tumor microenvironment in liver metastases was governed by the β-catenin activation status of the tumor. To this end, we analyzed CD8 and FoxP3 immunohistochemical expression against β-catenin expression status of the tumor in a cohort of 52 liver samples with metastatic carcinoma.

A Clinicopathological Study of Young-onset Hepatocellular Carcinoma.

Background/aim: The aim of this study was to describe the clinicopathological features of hepatocellular carcinoma (HCC) diagnosed at 40 years of age or below.

Materials And Methods: Expression of CK19, Glypican-3 and β-catenin was assessed in clinical samples by immunohistochemistry (IHC). IHC expression was correlated with clinicopathological parameters.

Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment.

Objective: We examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.

Design: The present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4-9 4 weekly doses of MD ARC-520 and entecavir.

Anti-tumour effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a biologically aggressive cancer. Targeted therapy is in need to tackle challenges in the treatment perspective. A growing body of evidence suggests a promising role of pharmacological inhibition of PIM (proviral integration site for Moloney murine leukaemia virus) kinase in some human haematological and solid cancers.

Among Patients with Undetectable Hepatitis B Surface Antigen and Hepatocellular Carcinoma, a High Proportion Has Integration of HBV DNA into Hepatocyte DNA and No Cirrhosis.

Background & Aims: In some individuals with undetectable serum levels of hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA can still be detected in serum or hepatocytes and HBV replicates at low levels-this is called occult HBV infection (OBI). OBI has been associated with increased risk of hepatocellular carcinoma (HCC). We investigated the incidence of OBI in patients with HCC and other liver diseases.

Deregulated GATA6 modulates stem cell-like properties and metabolic phenotype in hepatocellular carcinoma.

Accumulating evidence illustrates the significance of cell plasticity in the molecular biology of liver cancer. Reprogramming of mature parenchymal cells to a less differentiated state by key molecular targets contributes to the pathogenesis of hepatocellular carcinoma (HCC). Hereby, we investigated the role of GATA6, a transcription factor implicated in hepatocyte lineage specification, in HCC.

IRAK1 Augments Cancer Stemness and Drug Resistance via the AP-1/AKR1B10 Signaling Cascade in Hepatocellular Carcinoma.

Frequent relapse and drug resistance in patients with hepatocellular carcinoma (HCC) can be attributed to the existence of tumor-initiating cells (TIC) within the tumor bulk. Therefore, targeting liver TICs may improve the prognosis of these patients. From transcriptome sequencing of 16 pairs of clinical HCC samples, we report that interleukin-1 receptor-associated kinase 1 (IRAK1) in the TLR/IRAK pathway is significantly upregulated in HCC.

Cripto-1 contributes to stemness in hepatocellular carcinoma by stabilizing Dishevelled-3 and activating Wnt/β-catenin pathway.

Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness.

Deregulation of Frizzled Receptors in Hepatocellular Carcinoma.

G protein-coupled receptors (GPCRs) have a substantial role in tumorigenesis and are described as a "cancer driver". Aberrant expression or activation of GPCRs leads to the deregulation of downstream signaling pathways, thereby promoting cancer progression. In hepatocellular carcinoma (HCC), the Wnt signaling pathway is frequently activated and it is associated with an aggressive HCC phenotype.

Expression of hepatic progenitor cell markers in acute cellular rejection of liver allografts-An immunohistochemical study.

Background: Hepatic progenitor cells (HPC) are induced following liver injury to facilitate regeneration. Acute cellular rejection (ACR) is a common complication after liver transplantation as a result of immune-mediated liver injury. In this study, we characterized HPC phenotype in liver allograft biopsy with ACR.

Nuclear Met promotes hepatocellular carcinoma tumorigenesis and metastasis by upregulation of TAK1 and activation of NF-κB pathway.

Presence of Met receptor tyrosine kinase in the nucleus of cells has been reported. However, the functions of Met which expresses in the nucleus (nMet) remain elusive. In this study, we found that nMet was increased in 89% of HCC tumorous tissues when compared with the corresponding non-tumorous liver tissues.

Variation of stemness markers expression in tumor nodules from synchronous multi-focal hepatocellular carcinoma - an immunohistochemical study.

Background: Advancing knowledge in molecular pathogenesis of hepatocellular carcinoma (HCC) opens up new horizons in the diagnostic, prognostic and therapeutic perspectives. Assessing the expression of molecular targets prior to definitive treatment is gaining importance in clinical practice. In this study, we investigated the variation in expression pattern of stemness markers in synchronous multi-focal HCC.

Liver allograft biopsies with histological cholestasis: a clinicopathological study of 254 cases from a single centre.

Aims: Liver allograft biopsy is important in the management of liver transplant (LT) recipients. Cholestasis is an indicator of liver dysfunction, and histological evidence of cholestasis can be observed in a wide range of pathological entities in the post-LT setting. In this study, we describe the clinicopathological features and significance of liver allograft biopsies with histological cholestasis over 11 years in our centre.

Secretory Stanniocalcin 1 promotes metastasis of hepatocellular carcinoma through activation of JNK signaling pathway.

The hypoxic microenvironment is well-characterized in hepatocellular carcinoma (HCC). Delineation of hypoxia-responsive events is an integral part to understand the pathogenesis of HCC. We studied the functional role and clinical relevance of Stanniocalcin 1 (STC1), a hypoxia-induced molecular target, in HCC.

Stearoyl-CoA desaturase regulates sorafenib resistance via modulation of ER stress-induced differentiation.

Background & Aims: We investigated the functional role and clinical significance of stearoyl-CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulating liver tumor-initiating cells (T-ICs) and sorafenib resistance, with the aim of developing a novel therapeutic strategy against hepatocellular carcinomas (HCCs).

Methods: We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize the functional roles of SCD1 in regulating liver T-ICs and sorafenib resistance.

SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop.

Objective: We investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness.

Design: HCC cancer stemness was analysed by self-renewal ability, chemoresistance, expression of stemness-related genes and cancer stem cell (CSC) marker-positive cell population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level was examined with quantitative PCR in human paired HCCs.

Mechanisms through Which Hypoxia-Induced Caveolin-1 Drives Tumorigenesis and Metastasis in Hepatocellular Carcinoma.

In solid tumors, hypoxia triggers an aberrant vasculogenesis, enhances malignant character, and elevates metastatic risk. The plasma membrane organizing protein caveolin-1 (Cav1) is increased in a variety of cancers, including hepatocellular carcinoma (HCC), where it contributes to metastatic capability. However, the reason for elevation of Cav1 in tumor cells and the mechanistic basis for its contributions to metastatic risk are not fully understood.

Molecular Pathogenesis of Hepatocellular Carcinoma.

The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. The next-generation sequencing technology is facilitating the global and systematic evaluation of molecular landscapes in HCC. There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development.

Hypoxia induces myeloid-derived suppressor cell recruitment to hepatocellular carcinoma through chemokine (C-C motif) ligand 26.

Unlabelled: A population of stromal cells, myeloid-derived suppressor cells (MDSCs), is present in tumors. Though studies have gradually revealed the protumorigenic functions of MDSCs, the molecular mechanisms guiding MDSC recruitment remain largely elusive. Hypoxia, O2 deprivation, is an important factor in the tumor microenvironment of solid cancers, whose growth often exceeds the growth of functional blood vessels.

Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling.

Sox9, an SRY-related HMG box transcription factor, is a progenitor/precursor cell marker of the liver expressed during embryogenesis and following liver injury. In this study, we investigated the role of Sox9 and its molecular mechanism with reference to stemness properties in hepatocellular carcinoma (HCC). Here, we observed upregulation of Sox9 in human HCC tissues compared with the non-tumorous liver counterparts (p < 0.