Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease

Noah T. Zinkin, Franck Grall, Killimangalam Bhaskar, Hasan H Otu, Dimitrios Spentzos, Brett Kalmowitz, Meghan Wells, Manuel Guerrero, John M. Asara, Towia A. Libermann, Nezam H. Afdhal

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Abstract

Purpose: Proteomic profiling using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) enables the identification of biomarkers for cancer. We evaluated the sensitivity and specificity of SELDI-TOF MS for detection of established hepatocellular cancer (HCC) and compared it against α-fetoprotein (AFP), Lens culinaris agglutinin - reactive AFP (AFP-L3), and prothrombin induced by vitamin K absence-II (PIVKA-II). Experimental Design: Forty-one patients with HCC and 51 patients with hepatitis C cirrhosis were enrolled. Serum was analyzed by SELDI-TOF MS using three Ciphergen protein array types. Results: An 11-peak algorithm for HCC detection was identified. Using the AFP cutoff of 20 ng/mL, the sensitivity was 73% and the specificity was 71%. Using the AFP-L3 cutoff of 10% yielded a sensitivity of 63% and a specificity of 94%. Using the PIVKA-II cutoff of 125 milliabsorbance units (mAU), the sensitivity was 84% and the specificity was 69%. Overall, the sensitivity and specificity of SELDI-TOF MS for HCC were 79% and 86%, respectively. In multivariate analysis, the 11-peak SELDI profile was predictive of HCC independent of AFP, PIVKA, and AFP-L3. Among eight patients with the largest tumor size of <2 cm, SELDI-TOF MS correctly identified seven whereas AFP, AFP-L3, and PIVKA-II identified only three, one, and one, respectively. One of the 11 peaks in the SELDI-TOFMS 11-peak predictor from SELDI-TOF MS was identified as cystatin C. Conclusions: SELDI-TOF MS accurately distinguished patients with HCC from those with hepatitis C virus cirrhosis, was more accurate than traditional biomarkers in identifying small tumors, and should be further evaluated.

Original languageEnglish (US)
Pages (from-to)470-477
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number2
DOIs
StatePublished - Jan 15 2008

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Fetal Proteins
Proteomics
Liver Diseases
Hepatocellular Carcinoma
Chronic Disease
Biomarkers
Liver Neoplasms
Mass Spectrometry
Lasers
Serum
Vitamin K
Prothrombin
Fibrosis
Cystatin C
Sensitivity and Specificity
Protein Array Analysis
Hepatitis C
Tumor Biomarkers
Hepacivirus
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zinkin, N. T., Grall, F., Bhaskar, K., Otu, H. H., Spentzos, D., Kalmowitz, B., ... Afdhal, N. H. (2008). Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clinical Cancer Research, 14(2), 470-477. https://doi.org/10.1158/1078-0432.CCR-07-0586

Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. / Zinkin, Noah T.; Grall, Franck; Bhaskar, Killimangalam; Otu, Hasan H; Spentzos, Dimitrios; Kalmowitz, Brett; Wells, Meghan; Guerrero, Manuel; Asara, John M.; Libermann, Towia A.; Afdhal, Nezam H.

In: Clinical Cancer Research, Vol. 14, No. 2, 15.01.2008, p. 470-477.

Research output: Contribution to journalArticle

Zinkin, NT, Grall, F, Bhaskar, K, Otu, HH, Spentzos, D, Kalmowitz, B, Wells, M, Guerrero, M, Asara, JM, Libermann, TA & Afdhal, NH 2008, 'Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease', Clinical Cancer Research, vol. 14, no. 2, pp. 470-477. https://doi.org/10.1158/1078-0432.CCR-07-0586
Zinkin, Noah T. ; Grall, Franck ; Bhaskar, Killimangalam ; Otu, Hasan H ; Spentzos, Dimitrios ; Kalmowitz, Brett ; Wells, Meghan ; Guerrero, Manuel ; Asara, John M. ; Libermann, Towia A. ; Afdhal, Nezam H. / Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 2. pp. 470-477.
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abstract = "Purpose: Proteomic profiling using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) enables the identification of biomarkers for cancer. We evaluated the sensitivity and specificity of SELDI-TOF MS for detection of established hepatocellular cancer (HCC) and compared it against α-fetoprotein (AFP), Lens culinaris agglutinin - reactive AFP (AFP-L3), and prothrombin induced by vitamin K absence-II (PIVKA-II). Experimental Design: Forty-one patients with HCC and 51 patients with hepatitis C cirrhosis were enrolled. Serum was analyzed by SELDI-TOF MS using three Ciphergen protein array types. Results: An 11-peak algorithm for HCC detection was identified. Using the AFP cutoff of 20 ng/mL, the sensitivity was 73{\%} and the specificity was 71{\%}. Using the AFP-L3 cutoff of 10{\%} yielded a sensitivity of 63{\%} and a specificity of 94{\%}. Using the PIVKA-II cutoff of 125 milliabsorbance units (mAU), the sensitivity was 84{\%} and the specificity was 69{\%}. Overall, the sensitivity and specificity of SELDI-TOF MS for HCC were 79{\%} and 86{\%}, respectively. In multivariate analysis, the 11-peak SELDI profile was predictive of HCC independent of AFP, PIVKA, and AFP-L3. Among eight patients with the largest tumor size of <2 cm, SELDI-TOF MS correctly identified seven whereas AFP, AFP-L3, and PIVKA-II identified only three, one, and one, respectively. One of the 11 peaks in the SELDI-TOFMS 11-peak predictor from SELDI-TOF MS was identified as cystatin C. Conclusions: SELDI-TOF MS accurately distinguished patients with HCC from those with hepatitis C virus cirrhosis, was more accurate than traditional biomarkers in identifying small tumors, and should be further evaluated.",
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AU - Wells, Meghan

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