title: Cytokine levels contribute to the pathogenesis of minimal hepatic encephalopathy in patients with hepatocellular carcinoma via STAT3 activation.
abstract: Hepatocellular carcinoma (HCC) patients were grouped according to the degree of encephalopathy, with healthy volunteers as controls. We investigated clinical presentation, protein and mRNA expression of 14 cytokines, and activation of six STAT proteins, the downstream signaling mediators. Levels of all 14 cytokines were significantly elevated in HCC patients with clinical hepatic encephalopathy. Statistical analysis showed that levels of IL-1β, IL-6, IFNγ, IL-17α, IFNλ2 and IFNλ3 were correlated with minimal hepatic encephalopathy (MHE). Multivariate regression analysis identified serum IL-6, IFNλ3 and IL-17α as independent risk factors for MHE. Increased mRNA levels of IL-6 and IFNγ were associated with MHE. Among the STAT proteins examined, only STAT3 was elevated in MHE. Treatment with a STAT3 inhibitor protected neurons from cytokine-induced apoptosis in vitro. In conclusion, this study identified potential biomarkers for MHE in HCC. The cytokines investigated may induce neural apoptosis via STAT3 in the pathogenesis of MHE in HCC.
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for Liver Transplantation, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Center for Liver Transplantation, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Severe Liver Disorders, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.|Minimally Invasive Therapy Center of Liver Cancer, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D016207:Cytokines; D050796:STAT3 Transcription Factor