Protein Biomarkers for Early Detection and Prognostication in Hepatocellular Carcinoma (HCC)
Up to 40% of HCC patients have normal AFP. Moreover, AFP can also be elevated in patients
with cirrhosis or exacerbation of chronic hepatitis. Prospective studies evaluating the
value of AFP in HCC surveillance have reported sensitivities of 39-64%, specificity of
76-91% and positive predictive values of 9 -32% 9-11.
Recently, a small handful of biomarkers were identified in the blood of 49 HCC patients by
SELDI / MS proteomic analysis of their blood with specificity and sensitivity both at 90%
12, 13. These were truncated complement C3a, albumin, B2 microglobulin, and histidine-rich
glycoprotein. In addition, insulin growth factor (IGF) and its binding protein have been
shown to be novel biomarkers of HCC 14-17. A larger prospective study is necessary to
validate these findings.
Other investigators have also used Surface-enhanced laser desorption / ionization
time-of-flight mass spectrometry (SELDI) to study proteomics in HCC. Most of the studies
included small numbers of patients and did not include independent test set or report on
reproducibility most of the time. Thus, controversies continue on both the technology of
SELDI and validation of the findings. Nevertheless, Ward et al reported that Kappa and Lumda
immunoglobulin light chains were elevated by an average pf 50% in the serum of HCC patients
(p < 0.001, sensitivity 94%, specificity 86%) with Hepatitis C related cirrhosis 18.
Schwegler et al reported that SELDI-TOF MS profiling of serum can distinguish chronic
Hepatitis C from HCV- related HCC with a sensitivity of 61% and a specificity of 76%.
Sensitivity and specificity can be improved with the addition of AFP, des-gamma
carboxyprothrombin, and GP73 19. Other reports also indicated potential marker of heat-shock
protein 27 20 and complement C3a 21. However, all studies lack prospective and longitudinal
follow-up with multiple serum samples from same patient. Our trial is designed to test the
changes of proteomic overtime to identify the earliest possible biomarkers for HCC.
Time Perspective: Prospective
Alex Chang, MD
Johns Hopkins SIngapore International Medical Center
Singapore: Domain Specific Review Boards