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Aim: To explore the prognostic value of clusterin (CLU) in hepatocellular carcinoma (HCC) patients treated with oxaliplatin (OXA)., Methods: Relative expression of plasma CLU mRNA was examined via fluorescence quantitative real-time PCR (qRT-PCR), and CLU protein level in tissue samples was detected through immunohistochemistry. Chi-square test was used to analyze the relationship between CLU mRNA expression and clinical features of HCC patients treated with OXA. Kaplan-Meier method was performed to assess overall survival for the patients, and prognostic value of CLU in HCC patients was estimated via Cox regression analysis., Results: CLU expression in plasma and tissue specimens was significantly higher among HCC patients than in non-malignant controls (P < 0.001 for both). Moreover, elevated CLU mRNA was closely related to tumor stage, lymph node metastasis and response to OXA (P < 0.05). HCC patients with high CLU expression showed poor response to OXA. In addition, low CLU levels predicted long overall survival time among the study subjects (20.8 vs. 36.6 months, P < 0.001). CLU was an independent prognostic indicator for HCC patients treated with OXA (HR = 2.587, 95%CI = 1.749-3.828, P < 0.001)., Conclusion: CLU may be a novel prognostic marker for HCC patients treated with OXA., (© 2020 The Author(s).)

The upregulation of secretory clusterin (sCLU) is associated with tumor progression by contributing to angiogenesis, chemo-resistance, cell survival, and metastasis. However, its diagnostic or prognostic values for hepatocellular carcinoma (HCC) still remain to be clarified. The average serum sCLU level analyzed by an enzyme-linked immunosorbent assay was significantly higher (P < 0.001) in HCC patients than that in any of cases with cirrhosis, chronic hepatitis, or healthy control. The area under receiver operating characteristic curve and diagnostic sensitivity were 0.75 and 74.7 % in sCLU, and 0.74 and 58.7 % in α-fetoprotein (AFP), respectively. The combining detections of sCLU and AFP rose up to 90.7 % for HCC diagnosis. In liver, sCLU by immunohistochemistry was significantly higher (P < 0.001) in the HCC (77.3 %) group than that in their para-cancerous group (33.3 %). Abnormal serum or tissue sCLU expression was closely associated with tumor-node-metastasis (TNM) classification of malignant tumors and lymph node metastasis, as an independent prognosis factor (hazard ratio, 2.287; 95 % confidence interval, 1.044-5.007; P = 0.039), and higher sCLU expression significantly correlated (χ (2) = 4.252, P = 0.039) with poor survival of HCC patients analyzed by multivariate Cox regression or Kaplan-Meier method, suggesting that abnormal sCLU expression associated with tumor progression could be a potential diagnostic and prognostic biomarker for HCC.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Metastasis is the major concern that causes death in HCC. The goal of this study was to identify tumor-derived proteins in serum during HCC metastasis using an orthotopic xenograft tumor model and explore the role of key protein in HCC metastasis. Serum samples collected from HCCLM3-R metastatic HCC tumor model at specific stages of metastasis (1 wk, 3 wks and 6 wks) were subjected to iTRAQ labeling followed by 2DLC-ESI-MS/MS analysis. Twenty tumor-derived proteins were identified through human specific peptides. Secretory clusterin (sCLU), which was significantly upregulated during cancer progression and metastasis, was chosen for further study. The expression of sCLU was significantly higher in metastatic HCC cell lines and samples from metastatic HCC patients. ShRNA-mediated down-regulation of sCLU resulted in a reduced migratory capacity in HCC cell lines, as well as a reduction in pulmonary metastasis in vivo. Overexpression of sCLU in HepG2 cell line showed increased cell migratory ability. Further study found that sCLU contributed to HCC migration and epithelial-mesenchymal transition (EMT) in vitro, and metastasis in vivo. In addition, sCLU also plays an important role in the regulation of TGF-β1-smad3 signaling. These findings suggest that sCLU may promote HCC metastasis via the induction of EMT process and may be a candidate target for HCC therapy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is an increasing problem in Egypt. Clusterin has been reported to play a significant role in tumorigenesis., Aim: The aim of this study is to evaluate clusterin as a marker for evaluating diagnosis and metastasis potential of viral-related HCC., Methods: Eighty patients with HCC, 30 patients with liver cirrhosis, 30 patients with chronic hepatitis and 30 healthy controls were enrolled in study. Estimation of serum clusterin was done by enzyme linked immunosorbent assay., Results: Serum clusterin levels were significantly increased in patients with HCC. Serum clusterin was highly increased in patients with poorly differentiated tumor, capsular infiltration, portal vein invasion and lymph node infiltration. Receiver operator characteristic curve showed that clusterin had a greater area under curve value (0.95) than that of alpha fetoprotein (0.85). At cutoff value of 128 μg/mL, serum clusterin yielded (90%) sensitivity and (87%) specificity for predicting HCC., Conclusion: We concluded that clusterin is a promising useful marker for diagnosis of HCC. Clusterin might be deemed as a useful marker for predicting the progression and metastasis potential of HCC., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the differentially expressed serum proteins in patients with hepatoma carcinoma and identify a putative diagnostic marker., Method: The isobaric tags for relative and absolute quantitation (iTRAQ) labeling method and LC-MALDI-TOF/TOF MS detection method were used to quantify serum proteins in hepatocellular carcinoma patients (n =20) and healthy individuals (n =20). Real-time reverse transcription-polymerase chain reaction was used to verify the differentially expressed proteins by analyzing the corresponding mRNA expression levels in the hepatic carcinoma and healthy hepatocyte samples, as well as in 30 pairs of patient-matched hepatic carcinoma and adjacent normal tissue samples. Western blot analysis was used to verify the protein expression in hepatic carcinoma cells., Result: Fifty-one proteins were significantly differentially expressed between the hepatic carcinoma group and healthy controls. The iTRAQ protein profile showed that the serum level of clusterin was significantly lower in hepatoma carcinoma patients. The mRNA level of clusterin was 20-fold lower in hepatic carcinoma cells than in healthy hepatocytes, and was 2.38-fold lower in hepatoma tissues than that in adjacent normal tissues. The clusterin protein levels were significantly lower in hepatic carcinoma cells (8.06 vs normal hepatocytes: 27.81; P less than 0.01)., Conclusion: The serum expression of clusterin is significantly decreased in both serum and tissues of hepatic carcinoma patients. The relationship between hepatic carcinoma and clusterin should be evaluated in future studies.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the occurrence of HCC has more than doubled in the United States in the past decade. Early detection is considered key to reducing the mortality of HCC., Methods: Using two-dimensional gel electrophoresis and high-performance liquid chromatography we have analyzed the glycosylation of Apo-J from healthy controls, patients with liver cirrhosis, or those with HCC., Results: Apo-J in the serum from patients with HCC had decreased levels of (β-1,4) triantennary N-linked glycan compared with the healthy controls or patients with liver cirrhosis. We analyzed this change in an independent cohort of 76 patients with HCC, 32 with cirrhosis, and 43 infected with hepatitis C virus using the Datura stramonium lectin (DSL), which binds to (β-1,4) triantennary N-linked glycan. The level of DSL-reactive Apo-J allowed us to differentiate HCC from cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.852. When Apo-J was combined with other serum biomarkers such as α-fetoprotein (AFP) and fucosylated kininogen by using a multivariate logistic regression model, the AUROC increased to 0.944, a value much greater than that observed with AFP alone (AUROC of 0.765)., Conclusions: The glycosylation of Apo-J is a useful marker when used alone or in combination with outer makers for the early detection of HCC., Impact: The potential use of a combination of AFP, DSL-reactive Apo-J, and fucosylated kininogen as a biomarker of HCC would have great value in the management of patients with liver disease., (©2011 AACR.)

Background and Aim: Hepatocellular carcinoma (HCC) is a common human cancer worldwide. The levels of serum clusterin in HCC patients and its potential diagnostic significance is not clear. We aimed to evaluate the clinical use of serum clusterin levels as a surveillance tool for HCC with hepatitis B virus (HBV) related cirrhosis., Methods: Twenty-two cases of healthy subjects, 31 cases of HBV carriers, 26 patients with chronic hepatitis B, 29 patients with cirrhosis, and 76 patients with HCC were enrolled in this study. Serum levels of clusterin were measured by a sandwich enzyme-linked immunosorbent assay., Results: The serum clusterin levels in HCC patients were significantly lower than that in healthy, HBV carriers and chronic hepatitis B, but statistically higher than in cirrhosis patients. Receiver operator characteristic (ROC) curve indicated that a serum clusterin value of 50 microg/mL yielded the best sensitivity (91%) and specificity (83%) for differentiating HCC patients with HBV-related cirrhosis from those with HBV-related cirrhosis. The optimal alpha fetoprotein (AFP) cutoff value was 15 ng/mL and was inferior to the clusterin value of 50 microg/mL, the area under the ROC curves being 0.937 versus 0.781, respectively (P < 0.05)., Conclusions: Serum clusterin was more sensitive and specific than serum AFP for differentiating HCC patients with HBV-related cirrhosis from those with HBV-related liver cirrhosis, and may be a useful surveillance tool of HCC based on HBV-related cirrhosis.