Abstract
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 alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and prothrombin induced by vitamin K absence-II (PIVKA-II). 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. 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-TOF MS 11-peak predictor from SELDI-TOF MS was identified as cystatin C. 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.
Highlights
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 a-fetoprotein (AFP), Lens culinaris agglutinin ^ reactive AFP (AFP-L3), and prothrombin induced by vitamin K absence-II (PIVKA-II)
El-Serag et al showed that the incidence of HCC had increased from 1.8 per 100,000 to 2.5 per 100,000 over one decade and that most of this increase was attributable to infection with hepatitis C virus
The need for better tests for the diagnosis and screening of patients at risk of HCC is an important target for clinical researchers and one highlighted in the recent NIH roadmap for research in liver diseases [39]
Summary
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 a-fetoprotein (AFP), Lens culinaris agglutinin ^ reactive AFP (AFP-L3), and prothrombin induced by vitamin K absence-II (PIVKA-II). The sensitivity and specificity of SELDI-TOF MS for HCC were 79% and 86%, respectively. 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. Even with this screening regimen, many patients still present with either large HCC (>5 cm) or multifocal HCC (more than three lesions) or HCC that has invaded the portal vein or other critical structures. The most commonly used serum marker of HCC is AFP It has a reported sensitivity of 39% to 65% and specificity of 65% to 94% and has multiple limitations when applied to patients with HCV (9 – 11).
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