Surface enhanced laser desorption/ionization profiling: New diagnostic method of HBV-related hepatocellular carcinoma.
OBJECTIVE
To screen for serum biomarkers of HBV-related hepatocellular carcinoma (HCC) and HBV-related liver cirrhosis (LC) in an attempt to seek a new method for differential diagnosis of HCC and LC using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) techniques.


METHODS
Using SELDI-TOF-MS, serum proteins/peptide profiles on the immobilized metal ion affinity capture (IMAC) protein chips were obtained from 29 HCC patients and 30 LC patients. Discriminant analysis was carried out to establish new diagnostic methods using protein/peptide peaks with or without alpha-fetoprotein (AFP).


RESULTS
Forty-five protein/peptide peaks changed much more in the HCC group than they did in the LC group. Discriminant analysis using the Wilcoxon rank-sum test showed high sensitivity and specificity in distinguishing HCC from LC. The most significantly differentiating peak, 3892, offered 69.0% sensitivity, 83.3% specificity and 80% positive predictive value in distinguishing HCC and LC. Interestingly, six HCC patients with negative serum AFP were confirmed by peak 3892. The combination of multi-protein peaks (m/z = 9297, 29 941) with AFP offered an 82.8% sensitivity, 93.3% specificity and 92.3% positive predictive value, which was much better than AFP alone (P = 0.013).


CONCLUSIONS
Special proteins/peptides of serum may differentiate HBV-related HCC and HBV-related LC, indicating that SELDI-TOF-MS may be useful to distinguish HCC from LC with the proper discriminant analytical method. SELDI peak 3892 may be a complementary diagnostic marker to positive AFP for HCC and a potential marker for the diagnosis of AFP-negative HCC as well.
Wu
Cheng
C
Department of Gastroenterology, Changzheng Hospital, Shanghai 200003, China.
Wang
Zhanfeng
Z
Liu
Lijie
L
Zhao
Peng
P
Wang
Wenjing
W
Yao
Dingkang
D
Shi
Bing
B
Lu
Junhua
J
Liao
Ping
P
Yang
Yaning
Y
Zhu
Liang
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D003937:Diagnosis, Differential; D016002:Discriminant Analysis; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D016014:Linear Models; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D040081:Protein Array Analysis / Q000379:methods*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018709:Statistics, Nonparametric; D000509:alpha-Fetoproteins / Q000032:analysis
C097353:AFP protein, human; D015415:Biomarkers; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins