title: Systematic evaluation of circulating inflammatory markers for hepatocellular carcinoma.
abstract: A number of circulating inflammatory factors are implicated in the pathogenesis and prognostication of hepatocellular carcinoma (HCC). We aim to evaluate the prognostication of multiple serum inflammatory factors simultaneously and develop an objective inflammatory score for HCC.
  
  
  
  A prospective cohort of 555 patients with HCC with paired serum samples was accrued from 2009 to 2012. The blood levels of conventional inflammatory markers, namely C-reactive protein (CRP), albumin, neutrophils, lymphocytes and platelet, were determined, and 41 other exploratory markers were measured by a multiplex assay. The prognostication and interaction of markers were determined by univariate and multivarite analyses.
  
  
  
  The cohort was randomly divided into training cohort (n=139) and validation cohort (n=416). There were no differences in baseline characteristics between the two cohorts. In the training cohort, independent prognostic factors for overall survival included CRP (hazard ratio [HR] 1.107; P=.003), albumin (HR 0.953; P=.032) and interleukin-8 (HR=5.816; P<.001). We have modified the existing inflammation-based index (IBI) by adding serum interleukin-8 level. The modified IBI could stratify patients into four groups with distinct overall survival (P<.001). The results were also validated in the validation cohort. When compared with IBI and other conventional inflammatory markers, the modified IBI had better prognostic performance with higher c-index and homogeneity likelihood ratio chi-square.
  
  
  
  Among the conventional and exploratory circulating inflammatory markers, higher CRP, lower albumin and higher interleukin-8 were independent prognosticators. By combining these factors, a simple and accurate inflammatory index could be constructed.
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Clinical Oncology, Sir YK Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.|Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
authors: Stephen L
authors: SL
authors: Chan
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
authors: Anthony W H
authors: 0000-0002-1771-163X
authors: AW
authors: Chan
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
authors: Allen K C
authors: AK
authors: Chan
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.
authors: Peiyong
authors: P
authors: Jian
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Clinical Oncology, Sir YK Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors: Frankie
authors: 0000-0002-0566-3212
authors: F
authors: Mo
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Clinical Oncology, Sir YK Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors: Charles M L
authors: CM
authors: Chan
authors: Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors: Kevin
authors: K
authors: Mok
authors: Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors: Calvin
authors: C
authors: Liu
authors: Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
authors: Charing C N
authors: CC
authors: Chong
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Clinical Oncology, Sir YK Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors: Anthony T C
authors: AT
authors: Chan
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Clinical Oncology, Sir YK Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors: Tony
authors: T
authors: Mok
authors: State Key Laboratory in Oncology of South China, Hong Kong, China.|Department of Clinical Oncology, Sir YK Pao Center for Cancer, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors: Winnie
authors: W
authors: Yeo
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D005260:Female; D006723:Hong Kong; D006801:Humans; D007249:Inflammation / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D000075462:Serum Albumin, Human / Q000032:analysis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D016209:Interleukin-8; D002097:C-Reactive Protein; D000075462:Serum Albumin, Human
keywords: biomarker; circulation; cytokines; liver neoplasm