Serum Proteomics and Biomarkers in Hepatocellular Carcinoma and Chronic Liver Disease

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 a-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-TOF MS 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.The incidence of hepatocellular carcinoma (HCC) is on the rise in the United States (1 -3). Recently, 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 nearly all of this increase was attributable to infection with hepatitis C virus (HCV; ref. 2). Once cirrhosis has developed, retrospective studies have suggested that patients will develop either hepatic decompensation or HCC at a rate of 2% to 7% per year (4 -8). The general practice among many physicians has been to screen for HCC using ultrasound and serum a-fetoprotein (AFP) levels at 3-month to 6-month intervals.However, 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 limitations of ultrasound, the primary radiologic screening modality under current use, include its operator dependence and its poor ability to differentiate malignant from benign nodules in the small cirrhotic liver. Although imaging with triphasic computed tomography scan and magnetic resonance imaging with i.v. gadolinium can improve the diagnostic accuracy, these techniques are time consuming and too expensive for widespread screening at the present time. Because outco...

XAGE-1b expression is associated with the diagnosis and early recurrence of hepatocellular carcinoma

“…Serum XAGE-1b expression in human HCC patients. Serum tumor markers have been widely studied in HCC diagnosis and prognosis (17)(18)(19)(20). Thus, the serum XAGE-1b levels and the associations of its expression with HCC diagnosis and prognosis were further analyzed.…”

The Role of Circulating MicroRNAs as Markers of Disease Progression in Hepatitis C Virus Infected Egyptian Patients

“…Alpha-Fetoprotein (AFP) has mainly been used for diagnosis of HCC; however, its sensitivity and specificity are not satisfying that the Practice Guidelines of the American Association for the Study of Liver Diseases (AASLD) has rejected its use, since 2010, whether for the surveillance or the diagnosis of HCC [4].…”

Radiomics and circulating tumor cells: personalized care in hepatocellular carcinoma?

“…Proteomics is a similarly evolving field aiming to identify the complete proteome, including post-translational modifications. Small initial studies have revealed some positive findings, for example, an eleven peptide signature reported to have a better sensitivity and specificity for HCC than traditional serum markers (AFP and prothrombin induced by vitamin K absence-II [PIVKA-II]) (32). It remains to be seen whether these small studies can be reproduced on a larger scale and developed into a practical, clinical assay.…”