Biomarker identification in human pancreatic cancer sera.
OBJECTIVE
The aim of this study is to identify biomarkers in sera of pancreatic cancer patients using mass spectrometry (MS) approaches.


METHODS
Sera from patients diagnosed with pancreatic adenocarcinoma and sera from normal volunteers were subjected to gel electrophoresis to resolve and quantify differences in protein levels. Protein bands that differed quantitatively were digested with trypsin, and peptides were identified by electrospray ionization (ESI) ion-trap tandem MS. Mass spectra were also collected directly from pancreatic cancer sera as well as healthy control sera using ESI-MS.


RESULTS
Three large-mass proteins were found to be elevated in pancreatic cancer sera versus normal sera, alpha-2 macroglobulin, ceruloplasmin, and complement 3C. Complement 3C is a major regulator of inflammatory responses. The ESI-MS of human pancreatic cancer sera versus normal sera revealed greater heterogeneity in cancer sera than control sera, especially in the low-mass region. Bootstrapping statistical analysis identified 20 low-mass serum peaks that correlated with control sera and 20 different peaks that correlated with pancreatic cancer sera.


CONCLUSIONS
The fact that inflammation-sensitive proteins were identified as increased in pancreatic cancer sera supports the hypothesis that inflammatory-driven processes are involved in pancreatic carcinogenesis. Liquid ESI-MS analyses of sera hold promise for future pancreatic cancer blood tests as well as for understanding mechanisms of pancreatic carcinogenesis. The variability observed between the low-mass regions of normal versus pancreatic cancer spectra may aid in diagnosis and therapy.
Hanas
Jay S
JS
Department of Biochemistry & Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA. jay-hanas@ouhsc.edu
Hocker
James R
JR
Cheung
John Y
JY
Larabee
Jason L
JL
Lerner
Megan R
MR
Lightfoot
Stan A
SA
Morgan
Daniel L
DL
Denson
Kent D
KD
Prejeant
Kristi C
KC
Gusev
Yuiry
Y
Smith
Brenda J
BJ
Hanas
Rushie J
RJ
Postier
Russell G
RG
Brackett
Daniel J
DJ
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D002570:Ceruloplasmin / Q000032:analysis / Q000378:metabolism; D015932:Complement C3c / Q000032:analysis / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization; D014357:Trypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000032:analysis / Q000378:metabolism
D014408:Biomarkers, Tumor; D000511:alpha-Macroglobulins; D015932:Complement C3c; D002570:Ceruloplasmin; D014357:Trypsin