IL-6, through p-STAT3 rather than p-STAT1, activates hepatocarcinogenesis and affects survival of hepatocellular carcinoma patients: A cohort study
Journal
BMC Gastroenterology
Journal Volume
15
Journal Issue
1
Date Issued
2015
Author(s)
Abstract
Background: Biologic activities of functional mediators activate downstream transducers regulating inflammation and carcinogenesis. Correlation among mediators (IL-6, IL-27, TNF-α, and VEGF) with STAT proteins at diverse clinical-pathologic stages of hepatocellular carcinoma (HCC) remains limited. Methods: Serum mediators assayed from 147 untreated HCC cases (HCC-total group) included 70 HBV-infected (HCC-HBV group), 64 HCV-infected (HCC-HCV group), and 13 without HBV-/HCV-infection (HCC-NBNC group). Another 156 non-HCC individuals comprised 54 healthy individuals (HG) and 102 chronic hepatitis patients (CH-total group) as control group. To correlate with serum mediators, 86-paired liver tissues (CH: 52 and HCC: 34 cases) served for p-STATs proteins immunostain. Results: Although four mediators (IL-6, IL-27, TNF-α, and VEGF) significantly over-expressed, IL-6 presented the strongest correlation in HCC-total versus CH-total or HG groups (HCC-total versus CH-total: P<0.001; HCC-total versus HG: P<0.001). Over-expressed IL-6 concentration linked with poor liver function (Albumin: r=-0.383, P<0.001; Bilirubin: r=0.280, P=0.001; INR: r=0.299, P<0.001; AST: 0.212, P=0.016), tumor progression (TNM system: r=0.370; P<0.001), clinical condition severity (BCLC system: r=0.471; P<0.001; terminal- versus early-stage HCC, P=0.001; advanced- versus early-stage HCC, P=0.007; terminal- versus intermediate- stage HCC P=0.003; advanced- versus intermediate-stage HCC P=0.019), and 6-month mortality (P=0.024). Likewise, serum IL-6 (r=0.501, P=0.003) as compared to IL-27 (r=0.052, P=0.770), TNF-α(r=0.019, P=0.917), and VEGF (r=0.096, P=0.595) expression reflected positive correlation with activation of tissues p-STAT3 rather than p-STAT1. Conclusions: Serum IL-6, through p-STAT3 rather than p-STAT1 signal pathway, affected hepatic function, tumor progression, and determine HCC patient survival. ? Kao et al.; licensee BioMed Central.
Subjects
Chronic hepatitis; Hepatocellular carcinoma; IL-6; p-STAT3
SDGs
Other Subjects
albumin; aspartate aminotransferase; bilirubin; interleukin 27; interleukin 6; STAT1 protein; STAT3 protein; tumor necrosis factor alpha; vasculotropin; interleukin 27; interleukin 6; STAT1 protein; STAT1 protein, human; STAT3 protein; STAT3 protein, human; tumor necrosis factor; vasculotropin A; adult; advanced cancer; aged; Article; bioassay; cancer growth; cancer mortality; cancer staging; cancer survival; chronic hepatitis; cohort analysis; controlled study; disease association; disease severity; female; hepatitis B; hepatitis C; human; human tissue; international normalized ratio; liver carcinogenesis; liver cell carcinoma; liver function; major clinical study; male; protein blood level; protein expression; signal transduction; upregulation; blood; carcinogenesis; chemistry; chronic hepatitis B; chronic hepatitis C; complication; liver cell carcinoma; liver tumor; metabolism; middle aged; mortality; pathology; phosphorylation; Adult; Aged; Carcinogenesis; Carcinoma, Hepatocellular; Cohort Studies; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Interleukin-27; Interleukin-6; Liver Neoplasms; Male; Middle Aged; Phosphorylation; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A
Publisher
BioMed Central Ltd.
Type
journal article