Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors.
OBJECTIVE
Late diagnosis of colorectal carcinoma results in a significant reduction of average survival times. Yet despite screening programs, about 70% of tumors are detected at advanced stages (International Union Against Cancer stages III/IV). We explored whether detection of malignant disease would be possible through identification of tumor-specific protein biomarkers in serum samples.


METHODS
A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Candidate proteins were identified and their expression levels were validated in independent sample sets using a specific immunoassay (enzyme-linked immunosorbent assay).


RESULTS
By using class comparison and custom-developed algorithms we identified several m/z values that were expressed differentially between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a-desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6% were classified as normal.


CONCLUSIONS
Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (P < .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer.
Habermann
Jens K
JK
Genetics Branch, National Cancer Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
Roblick
Uwe J
UJ
Luke
Brian T
BT
Prieto
Darue A
DA
Finlay
William J J
WJ
Podust
Vladimir N
VN
Roman
John M
JM
Oevermann
Elisabeth
E
Schiedeck
Thomas
T
Homann
Nils
N
Duchrow
Michael
M
Conrads
Thomas P
TP
Veenstra
Timothy D
TD
Burt
Stanley K
SK
Bruch
Hans-Peter
HP
Auer
Gert
G
Ried
Thomas
T
D000236:Adenoma / Q000097:blood* / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000706:Anaphylatoxins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D015926:Complement C3a / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000706:Anaphylatoxins; D014408:Biomarkers, Tumor; D015926:Complement C3a