title: Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma.
abstract: Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel.Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers.When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL." The combination of "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%" had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL," with this also being the case when the cut-off value of AFP and AFP-L3 was changed.Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.
authors.affiliation: Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon Biostatistical Consulting Unit Department of Laboratory Medicine, Soonchunhyang University, Seoul, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Jang
authors.forename: Soung Won
authors.initials: SW
authors.lastname: Jeong
authors.forename: Young Kyu
authors.initials: YK
authors.lastname: Cho
authors.forename: Sae Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Sang Gyune
authors.initials: SG
authors.lastname: Kim
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Cha
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Deok
authors.initials: YD
authors.lastname: Cho
authors.forename: Hong Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Boo Sung
authors.initials: BS
authors.lastname: Kim
authors.forename: Suyeon
authors.initials: S
authors.lastname: Park
authors.forename: Hae In
authors.initials: HI
authors.lastname: Bang
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D037121:Plant Lectins; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D037121:Plant Lectins; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C033619:lentil lectin; C008208:acarboxyprothrombin; D011516:Prothrombin