Detection of hepatocellular carcinoma using glycomic analysis.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Goldman
Radoslav
R
Department of Oncology, Georgetown University, Washington, District of Columbia 20057-1469, USA. rg26@georgetown.edu
Ressom
Habtom W
HW
Varghese
Rency S
RS
Goldman
Lenka
L
Bascug
Gregory
G
Loffredo
Christopher A
CA
Abdel-Hamid
Mohamed
M
Gouda
Iman
I
Ezzat
Sameera
S
Kyselova
Zuzana
Z
Mechref
Yehia
Y
Novotny
Milos V
MV
D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood* / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D011134:Polysaccharides