Detection of hepatocellular carcinoma using glycomic analysis - PubMed (original) (raw)

Comparative Study

. 2009 Mar 1;15(5):1808-13.

doi: 10.1158/1078-0432.CCR-07-5261. Epub 2009 Feb 17.

Habtom W Ressom, Rency S Varghese, Lenka Goldman, Gregory Bascug, Christopher A Loffredo, Mohamed Abdel-Hamid, Iman Gouda, Sameera Ezzat, Zuzana Kyselova, Yehia Mechref, Milos V Novotny

Affiliations

Comparative Study

Detection of hepatocellular carcinoma using glycomic analysis

Radoslav Goldman et al. Clin Cancer Res. 2009.

Abstract

Purpose: Hepatocellular carcinoma (HCC) represents an increasing health problem in the United States. Serum alpha-fetoprotein, the currently used clinical marker, is elevated in only approximately 60% of HCC patients; therefore, the identification of additional markers is expected to have significant public health impact. The objective of our study was to quantitatively assess N-glycans originating from serum glycoproteins as alternative markers for the detection of HCC.

Experimental design: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for quantitative comparison of 83 N-glycans in serum samples of 202 participants (73 HCC cases, 77 age- and gender-matched cancer-free controls, and 52 patients with chronic liver disease). N-glycans were enzymatically released from serum glycoproteins and permethylated before mass spectrometric quantification.

Results: The abundance of 57 N-glycans was significantly altered in HCC patients compared with controls. The sensitivity of six individual glycans evaluated for separation of HCC cases from population controls ranged from 73% to 90%, and the specificity ranged from 36% to 91%. A combination of three selected N-glycans was sufficient to classify HCC with 90% sensitivity and 89% specificity in an independent validation set of patients with chronic liver disease. The three N-glycans remained associated with HCC after adjustment for chronic viral infection and other known covariates, whereas the other glycans increased significantly at earlier stages of the progression of chronic viral infection to HCC.

Conclusion: A set of three identified N-glycans is sufficient for the detection of HCC with 90% prediction accuracy in a population with high rates of hepatitis C viral infection. Further evaluation of a wider clinical utility of these candidate markers is warranted.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Figures

Fig. 1

Fig. 1

Average MALDI-TOF spectra in the mass range of 1.5 to 5.5 kDa in HCC cases (n = 73) and population controls (n = 77; inverted).

Fig. 2

Fig. 2

Area under the ROC curve (AuROC) for three glycans comparing a blinded validation set of HCC cases (n = 47) and CLD controls (n = 27).

Fig. 3

Fig. 3

Box plots comparing three selected glycans in the following patient groups: fibrosis (n = 22; A), cirrhosis (n = 25; B), and early HCC (stage I and II; n = 18; C). Both the fibrosis and cirrhosis groups are significantly different from the early-stage HCC at P < 0.05 as indicated in the figure.

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