Dataset Information

Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma.

ABSTRACT: Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC), most cases of which are related to either hepatitis B virus (HBV) or hepatitis C virus (HCV). Prior studies have examined differences in individual cytokine levels in patients with chronic liver disease, but comprehensive cytokine profiling data across different clinical characteristics are lacking. We examined serum cytokine profiles of 411 patients with HCC (n?=?102: 32% HBV, 54% HCV, 14% non-viral) and without HCC (n?=?309: 39% HBV, 39% HCV, 22% non-viral). Multiplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines. Random forest machine learning was used to obtain receiver operator characteristic curves and to determine individual cytokine importance using Z scores of mean fluorescence intensity for individual cytokines. Among HCC and non-HCC patients, cytokine profiles differed between HBV and HCV patients (area under curve (AUC) 0.82 for HCC, 0.90 for non-HCC). Cytokine profiles did not distinguish cirrhotic HBV patients with and without HCC (AUC 0.503) or HCV patients with and without HCC (AUC 0.63). In conclusion, patients with HBV or HCV infection, with or without HCC, have distinctly different cytokine profiles, suggesting potential differences in disease pathogenesis and/or disease characteristics.

SUBMITTER: Estevez J

PROVIDER: S-EPMC5605527 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma.

Estevez Jacqueline J Chen Vincent L VL Podlaha Ondrej O Li Biao B Le An A Vutien Philip P Chang Ellen T ET Rosenberg-Hasson Yael Y Jiang Zhaoshi Z Pflanz Stefan S Ge Dongliang D Gaggar Anuj A Nguyen Mindie H MH

Scientific reports 20170919 1

Cytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC), most cases of which are related to either hepatitis B virus (HBV) or hepatitis C virus (HCV). Prior studies have examined differences in individual cytokine levels in patients with chronic liver disease, but comprehensive cytokine profiling data across different clinical characteristics are lacking. We examined serum cytokine profiles of 411 patients with HCC (n = 102: 32% HBV, 54% HCV, 14% non- ...[more]

PMID: 28928388

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Project description:Sorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug's survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that serum cytokines levels could predict the survival of advanced HCC patients, as sorafenib targets signaling pathways activated in the tumor stromal microenvironment and potentially affects serum cytokine profiles.Of 143 patients with advanced-stage HCC, 104 who were recruited between 2003 and 2007 received hepatic arterial infusion chemotherapy (HAIC) that mainly targets tumor epithelial cells at S-phase (cohort 1); additionally, 39 recruited between 2010 and 2012 received sorafenib, which primarily targets the stromal vascular endothelial cells. Serum samples were collected and aliquoted prior to the treatment. Serum EGF, bFGF, HGF, IFN-?, IL-10, IL-12, IL-2, IL-4, IL-5, IL-6, IL-8, IP-10, MIG, PDGF-BB, SCF, SDF1, TGF-?, TGF-?, TNF-?, and VEGF-A were measured via enzyme-linked immunosorbent assays. The Modified Response Evaluation Criteria in Solid Tumors were used to assess tumor responses.The median survival time of HCC patients in cohorts 1 (HAIC-treated) and 2 (sorafenib-treated) were 12.0 and 12.4 months, respectively. Kaplan-Meier analysis revealed no significant survival differences between the 2 groups. Patients who survived more than 2 years after sorafenib treatment exhibited higher serum levels of IL-10, IL-12, TNF-a, IL-8, SDF-1, EGF, PDGF-BB, SCF, and TGF-?. Furthermore, cohort 2 patients with higher serum IL-5 (>12 pg/mL), IL-8 (>10 pg/mL), PDGF-BB (>300 pg/mL), and VEGF-A (>50 pg/mL) levels achieved longer survival; cohort 1 patients did not. Hierarchical cluster analysis of 6 cytokines robustly enriched for comparison analysis between cohorts 1 and 2 (IL-5, IL-8, TGF-?, PDGF-BB, CXCL9, and VEGF-A) revealed that elevation of these cytokines correlated with better survival when treated with sorafenib but not with HAIC.Patients who exhibited survival benefits owing to sorafenib treatment tended to present higher serum cytokines levels, potentially reflecting the activation of stromal signaling in the tumor microenvironment. Our study thus introduces novel biomarkers that may identify advanced HCC patients who may experience survival benefits with sorafenib treatment.

Dataset Information

Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma.

Publications

Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma.

Similar Datasets

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