Carcinogenesis Advance Access published online on August 27, 2007
Carcinogenesis, doi:10.1093/carcin/bgm177
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Candidate Markers for the Detection of Hepatocellular Carcinoma in Low Molecular Weight Fraction of Serum
R Goldman, H W Ressom, L Goldman, A Wang, R S Varghese, Y An, E Orvisky, C A Loffredo, F Seillier Moiseiwitsch, Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC
M Abdel-Hamid, Minia University and Viral Hepatitis Research Laboratory, NHTMRI, Cairo, Egypt
S K Drake, Clinical Chemistry Service, Department of Laboratory Medicine, NIH, Bethesda, MD
S A Eissa, I Gouda, National Cancer Institute, Cairo, Egypt
S Ezzat, Menoufiya University, Shibin El Kom, Egypt
Correspondence to: Radoslav Goldman, Georgetown University, LCCC Room S183, 3970 Reservoir Rd NW, Washington DC 20057-1469, Phone : 202-687-9868 ; Fax: 202-6871988 ; 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 HCV infection. Serum alpha fetoprotein is elevated in only approximately 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. MALDI-TOF 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 HBV infections. The marker candidates are independently predictive of HCC with areas under the ROC curve ranging from 63-93%. A combination of the six markers improves prediction accuracy to 100% sensitivity, 91% specificity, and 98% area under the ROC 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.
Received May 3, 2007; revised June 25, 2007; accepted July 22, 2007.