Discovery of serum biomarkers for pancreatic adenocarcinoma using proteomic analysis.
OBJECTIVE
The serum/plasma proteome was explored for biomarkers to improve the diagnostic ability of CA19-9 in pancreatic adenocarcinoma (PC).


METHODS
A Training Set of serum samples from 20 resectable and 18 stage IV PC patients, 54 disease controls (DCs) and 68 healthy volunteers (HVs) were analysed by surface-enhanced laser desorption and ionisation time-of-flight mass spectrometry (SELDI-TOF MS). The resulting protein panel was validated on 40 resectable PC, 21 DC and 19 HV plasma samples (Validation-1 Set) and further by ELISA on 33 resectable PC, 28 DC and 18 HV serum samples (Validation-2 Set). Diagnostic panels were derived using binary logistic regression incorporating internal cross-validation followed by receiver operating characteristic (ROC) analysis.


RESULTS
A seven-protein panel from the training set PC vs DC and from PC vs HV samples gave the ROC area under the curve (AUC) of 0.90 and 0.90 compared with 0.87 and 0.91 for CA19-9. The AUC was greater (0.97 and 0.99, P<0.05) when CA19-9 was added to the panels and confirmed on the validation-1 samples. A simplified panel of apolipoprotein C-I (ApoC-I), apolipoprotein A-II (ApoA-II) and CA19-9 was tested on the validation-2 set by ELISA, in which the ROC AUC was greater than that of CA19-9 alone for PC vs DC (0.90 vs 0.84) and for PC vs HV (0.96 vs 0.90).


CONCLUSIONS
A simplified diagnostic panel of CA19-9, ApoC-I and ApoA-II improves the diagnostic ability of CA19-9 alone and may have clinical utility.
Xue
A
A
Department of Surgery, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
Scarlett
C J
CJ
Chung
L
L
Butturini
G
G
Scarpa
A
A
Gandy
R
R
Wilson
S R
SR
Baxter
R C
RC
Smith
R C
RC
D000230:Adenocarcinoma / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D016632:Apolipoprotein A-I / Q000097:blood*; D053302:Apolipoprotein C-I / Q000097:blood*; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020033:Protein Isoforms / Q000097:blood; D040901:Proteomics / Q000379:methods*; D012016:Reference Values; D012044:Regression Analysis; D015203:Reproducibility of Results
D016632:Apolipoprotein A-I; D053302:Apolipoprotein C-I; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D020033:Protein Isoforms; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase