title: Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC.
  
  
  METHODS
  Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis.
  
  
  RESULTS
  The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034).
  
  
  CONCLUSIONS
  The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Jung
authors.affiliation: Soonchunhyang Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Soonchunhyang Medical Science Research Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Pathology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Susie
authors.initials: S
authors.lastname: Chin
authors.affiliation: Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Jun Chul
authors.initials: JC
authors.lastname: Chung
authors.affiliation: Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Moon Soo
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Moo-Jun
authors.initials: MJ
authors.lastname: Baek
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein
keywords: Hepatocellular carcinoma; Prognosis; Programmed cell death 1; Programmed cell death 1 ligand