title: Low utility of plasma Nociceptin/orphanin FQ in the diagnosis of hepatocellular carcinoma.
abstract: OBJECTIVE
  The utility of serum alpha-fetoprotein (alpha-FP) in the detection of hepatocellular carcinoma (HCC) is questionable. Very high circulating levels of nociceptin/orphanin FQ (N/OFQ), a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis.
  
  
  METHODS
  Plasma N/OFQ levels were measured by ELISA in 58 patients (28 HCC and 30 liver cirrhosis) and in 25 healthy controls. The values were correlated with clinical and laboratory features including alpha-FP. Spearman index, biserial correlation coefficient, non parametric combination (NPC) test and discriminant stepwise analysis were used for statistical evaluation of data.
  
  
  RESULTS
  The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. alpha-FP serum levels > 200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including alpha-FP. By NPC test, HCC and cirrhotic patients were different with regard to alpha-FP (P = 0.000) but not in terms of nociceptin (P = 0.595). By point biserial correlation, HCC presence was positively correlated with alpha-FP (rpb = 0.52, P = 0.000) but not with N/OFQ (rpb = 0.16, P = 0.157). In a discriminant analysis, alpha-FP was significant in the Wilks test (Y = -0.709 + 0.03 alpha-FP) and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than alpha-FP.
  
  
  CONCLUSIONS
  Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.
authors.affiliation: Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Clinica Medica, Pad. C, AOU, Via Consolare Valeria No. 1, Messina 98125, Italy. aldo.spadaro@unime.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Spadaro
authors.forename: Antonino
authors.initials: A
authors.lastname: Ajello
authors.forename: Carmelo
authors.initials: C
authors.lastname: Luigiano
authors.forename: Carmela
authors.initials: C
authors.lastname: Morace
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Resta
authors.forename: Grazia
authors.initials: G
authors.lastname: Berlinghieri
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
authors.forename: Claudio
authors.initials: C
authors.lastname: Scisca
authors.forename: Angela
authors.initials: A
authors.lastname: Alibrandi
authors.forename: Graziella
authors.initials: G
authors.lastname: D'Arrigo
authors.forename: Nunziata
authors.initials: N
authors.lastname: Alessi
authors.forename: Oscar
authors.initials: O
authors.lastname: Ferrau
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Freni
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018847:Opioid Peptides / Q000097:blood*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D000097629:Nociceptin
chemical_list: D014408:Biomarkers, Tumor; D018847:Opioid Peptides; D000097629:Nociceptin