Validation of a novel model for the early detection of hepatocellular carcinoma

Philip M. Hemken, Lori J. Sokoll, Xiaoqing Yang, Jianliang Dai, Debra Elliott, Susan H. Gawel, Michael Lucht, Ziding Feng, Jorge A Marrero, Sudhir Srivastava, Daniel W. Chan, Gerard J. Davis

Research output: Contribution to journalArticle

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Abstract

Background: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. Methods: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. Results: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95% CI 0.93-0.98), with a sensitivity of 93% and a specificity of 84% in the development cohort, and an AUC of 0.87 (95% CI 0.85-0.90), sensitivity of 74%, and specificity of 85% in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95% CI 0.81-0.88), sensitivity was 70%, and specificity was 86%. Conclusions: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.

Original languageEnglish (US)
Article number2
JournalClinical Proteomics
Volume16
Issue number1
DOIs
StatePublished - Jan 16 2019

Fingerprint

alpha-Fetoproteins
Vitamin K
Hepatocellular Carcinoma
Liver
Proteins
Biomarkers
Area Under Curve
Liver Diseases
Immunoassay
Case-Control Studies
Healthy Volunteers
Fibrosis
Sensitivity and Specificity
Serum

Keywords

  • Biomarker
  • Cancer
  • Des-gamma carboxyprothrombin
  • Early diagnosis
  • Liver

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Hemken, P. M., Sokoll, L. J., Yang, X., Dai, J., Elliott, D., Gawel, S. H., ... Davis, G. J. (2019). Validation of a novel model for the early detection of hepatocellular carcinoma. Clinical Proteomics, 16(1), [2]. https://doi.org/10.1186/s12014-018-9222-0

Validation of a novel model for the early detection of hepatocellular carcinoma. / Hemken, Philip M.; Sokoll, Lori J.; Yang, Xiaoqing; Dai, Jianliang; Elliott, Debra; Gawel, Susan H.; Lucht, Michael; Feng, Ziding; Marrero, Jorge A; Srivastava, Sudhir; Chan, Daniel W.; Davis, Gerard J.

In: Clinical Proteomics, Vol. 16, No. 1, 2, 16.01.2019.

Research output: Contribution to journalArticle

Hemken, PM, Sokoll, LJ, Yang, X, Dai, J, Elliott, D, Gawel, SH, Lucht, M, Feng, Z, Marrero, JA, Srivastava, S, Chan, DW & Davis, GJ 2019, 'Validation of a novel model for the early detection of hepatocellular carcinoma', Clinical Proteomics, vol. 16, no. 1, 2. https://doi.org/10.1186/s12014-018-9222-0
Hemken, Philip M. ; Sokoll, Lori J. ; Yang, Xiaoqing ; Dai, Jianliang ; Elliott, Debra ; Gawel, Susan H. ; Lucht, Michael ; Feng, Ziding ; Marrero, Jorge A ; Srivastava, Sudhir ; Chan, Daniel W. ; Davis, Gerard J. / Validation of a novel model for the early detection of hepatocellular carcinoma. In: Clinical Proteomics. 2019 ; Vol. 16, No. 1.
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abstract = "Background: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. Methods: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. Results: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95{\%} CI 0.93-0.98), with a sensitivity of 93{\%} and a specificity of 84{\%} in the development cohort, and an AUC of 0.87 (95{\%} CI 0.85-0.90), sensitivity of 74{\%}, and specificity of 85{\%} in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95{\%} CI 0.81-0.88), sensitivity was 70{\%}, and specificity was 86{\%}. Conclusions: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.",
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AU - Hemken, Philip M.

AU - Sokoll, Lori J.

AU - Yang, Xiaoqing

AU - Dai, Jianliang

AU - Elliott, Debra

AU - Gawel, Susan H.

AU - Lucht, Michael

AU - Feng, Ziding

AU - Marrero, Jorge A

AU - Srivastava, Sudhir

AU - Chan, Daniel W.

AU - Davis, Gerard J.

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N2 - Background: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. Methods: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. Results: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95% CI 0.93-0.98), with a sensitivity of 93% and a specificity of 84% in the development cohort, and an AUC of 0.87 (95% CI 0.85-0.90), sensitivity of 74%, and specificity of 85% in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95% CI 0.81-0.88), sensitivity was 70%, and specificity was 86%. Conclusions: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.

AB - Background: The biomarkers alpha-fetoprotein (AFP) and protein induced by vitamin K absence/antagonist-II (PIVKA-II) may be useful for detecting early-stage hepatocellular carcinoma (HCC). We evaluated the performance of AFP and PIVKA-II levels, alone and in combination with clinical factors, for the early detection of HCC. Methods: In a case-control study, serum AFP and PIVKA-II were measured using the ARCHITECT immunoassay analyzer system in a cohort of 119 patients with HCC, 215 patients with non-malignant liver disease, and 34 healthy subjects. Five predictive models for detecting HCC were developed based on age, gender, AFP, and/or PIVKA-II levels; the best model was validated in an independent cohort of 416 patients with HCC and 412 control subjects with cirrhosis. Results: In both cohorts, AFP and PIVKA-II concentrations were higher in patients with HCC compared to healthy controls and patients with non-malignant liver disease. The model that combined AFP and PIVKA-II, age, and gender had the highest AUC of 0.95 (0.95, 95% CI 0.93-0.98), with a sensitivity of 93% and a specificity of 84% in the development cohort, and an AUC of 0.87 (95% CI 0.85-0.90), sensitivity of 74%, and specificity of 85% in the validation cohort. When limiting the validation cohort to only early-stage HCC, the AUC was 0.85 (95% CI 0.81-0.88), sensitivity was 70%, and specificity was 86%. Conclusions: Compared to each biomarker alone, the combination of AFP and PIVKA-II with age and gender improved the accuracy of detecting HCC and differentiating HCC from non-malignant liver disease.

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