Carcinogenesis Advance Access originally published online on August 27, 2007
Carcinogenesis 2007 28(10):2149-2153; doi:10.1093/carcin/bgm177
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Candidate markers for the detection of hepatocellular carcinoma in low-molecular weight fraction of serum
Georgetown University, Lombardi Comprehensive Cancer Center, 3970 Reservoir Road Northwest, Washington, DC 20057, USA
1 Minia University and Viral Hepatitis Research Laboratory, NHTMRI, Cairo, Egypt
2 Clinical Chemistry Service, Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA
3 National Cancer Institute, Cairo, Egypt
4 Menoufiya University, Shibin El Kom, Egypt
* To whom correspondence should be addressed. Tel: +1 202 687 9868; Fax: +1 202 687 1988; Email: rg26{at}georgetown.edu
Hepatocellular carcinoma (HCC) represents an important public health problem in Egypt where up to 90% of HCC cases are attributable to hepatitis C viral (HCV) infection. Serum alpha-fetoprotein is elevated in only 
60% of HCC patients. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant public health implications worldwide. The objective of our study was to assess six candidate markers for detection of HCC identified by mass spectrometric analysis of enriched serum. The study examined 78 HCC cases and 72 age- and gender-matched cancer-free controls recruited from the Egyptian population. Matrix-assisted laser desorption–ionization time-of-flight mass spectrometric analysis of enriched low-molecular weight fraction of serum was used for identification of the candidate markers. Our analyses show that all six candidate markers are associated with HCC after adjustment for important covariates including HCV and hepatitis B viral infections. The marker candidates are independently predictive of HCC with areas under the receiver operating characteristic (AuROC) curve ranging from 63–93%. A combination of the six markers improves prediction accuracy to 100% sensitivity, 91% specificity and 98% AuROC curve in an independent test set of 50 patients. Two of the candidate markers were identified by sequencing as fragments of complement C3 and C4. In conclusion, a set of six peptides distinguished with high prediction accuracy HCC from controls in an Egyptian population with a high rate of chronic HCV infection. Further evaluation of these marker candidates for the diagnosis of HCC is needed.
Abbreviations: AFP, alpha-fetoprotein; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LMW, low-molecular weight; MALDI–TOF, matrix-assisted laser desorption–ionization time-of-flight; MS, mass spectrometry; PSO, particle swarm optimization; SVM, support vector machine
Received May 3, 2007; revised June 25, 2007; accepted July 22, 2007.