title: Plasma Level of Interleukin-35 as an Independent Prognostic Indicator in Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma is a major type of liver cancer with poor prognosis.
  
  
  
  The aim of the study was to determine the prognostic significance of plasma interleukin-35 level in hepatocellular carcinoma.
  
  
  
  A total of 153 hepatocellular carcinoma patients and 153 healthy controls were enrolled. Blood samples were obtained at admission. Plasma interleukin-35 level was analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and expression of Fas/FasL protein were detected by flow cytometry. The patients were followed up for 2 years. Poor prognosis was defined as death of hepatocellular carcinoma.
  
  
  
  The plasma levels of interleukin-35 were significantly higher in the patients than the controls (25.1 ± 13.1, 9.3 ± 6.3 pg/mL, P < 0.001). After adjusted for multiple confounding factors, the multivariate logistic regression analyses reported that high level of interleukin-35 (≥25.0 pg/mL) was associated with the poor prognosis in the patients (OR 6.63, 95 % CI 3.27-13.47). Compared with the patients with low level of interleukin-35 (<25.0 pg/mL), the patients with high level of interleukin-35 showed higher frequencies of CD4+CD25+FoxP3+ and CD3+Foxp3+ regulatory T cells (P < 0.001 and P < 0.001) and also showed higher apoptosis levels of CD8+ T cells (P < 0.001).
  
  
  
  Circulating interleukin-35 concentration might be an independent prognostic indicator in hepatocellular carcinoma. Such prognostic significance could be partly involved in the activation of regulatory T cell and the apoptosis of CD8+ T cell.
authors.affiliation: Department of Clinical Laboratory, Yishui Central Hospital, No. 17, Health Road, Yishui County, Linyi, 276400, Shandong, China.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Clinical Laboratory, Yishui Central Hospital, No. 17, Health Road, Yishui County, Linyi, 276400, Shandong, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Yishui Central Hospital, No. 17, Health Road, Yishui County, Linyi, 276400, Shandong, China.
authors.forename: Yucui
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, Yishui Central Hospital, No. 17, Health Road, Yishui County, Linyi, 276400, Shandong, China. chenlilidtsg@sina.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000328:Adult; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000378:metabolism / Q000401:mortality; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000378:metabolism / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; C418974:FOXP3 protein, human; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D019014:fas Receptor; C532417:interleukin-35, human
keywords: Apoptosis; Hepatocellular carcinoma; Interleukin-35; Prognosis; Regulatory T lymphocytes