title: Higher serum interleukin-17A levels as a potential biomarker for predicting early disease progression in patients with hepatitis B virus-associated advanced hepatocellular carcinoma treated with sorafenib.
abstract: Although sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib.
  
  
  
  Thirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled. Using a Luminex 200 system, 11 cytokines including interleukin-17A (IL-17A) were measured in baseline serum samples prior to sorafenib administration. Several clinical factors and the serum concentrations of the 11 cytokines were analyzed using Cox regression analysis.
  
  
  
  In the analysis of progression-free survival (PFS), older age (year; hazard ratio [HR]=1.07; 95% confidence interval [CI]=1.00-1.15; P=0.046) and higher baseline serum IL-17A level (>1.94pg/mL; HR=19.96; 95% CI=3.32-119.86; P=0.001) were identified as significant risk factors for early progression with good predictive power (Harrell's C=0.817, standard error estimates (se)=0.085). In the analysis of OS, higher Child-Pugh score (>5; HR=2.35, 95% CI=1.09-5.10, P=0.030) and lower serum baseline fibroblast growth factor-2 level (≤20.57pg/mL; HR=3.24, 95% CI=1.22-8.60, P=0.018) were identified as negative predictive factors for OS, even though the model did not have significant predictive power (Harrell's C=0.634, se=0.062).
  
  
  
  A higher serum IL-17A level is a potential biomarker for predicting poor PFS in patients with HBV-related advanced HCC treated with sorafenib.
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Human Genome Research & Bio-resource Center, Ajou University Medical Center, Suwon, Republic of Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Office of Biostatistics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Oh
authors.affiliation: Office of Biostatistics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Kang
authors.affiliation: Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jai Keun
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jei Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Bohyun
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Hwang
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Sun Gyo
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Kee Myung
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Byung Moo
authors.initials: BM
authors.lastname: Yoo
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: jaeyoun620@gmail.com.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Fibroblast growth factor-2; Hepatocellular carcinoma; Interleukin-17A; Prognosis; Sorafenib