title: Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors.
abstract: 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.
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Brian T
authors.initials: BT
authors.lastname: Luke
authors.forename: Darue A
authors.initials: DA
authors.lastname: Prieto
authors.forename: William J J
authors.initials: WJ
authors.lastname: Finlay
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Podust
authors.forename: John M
authors.initials: JM
authors.lastname: Roman
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oevermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Schiedeck
authors.forename: Nils
authors.initials: N
authors.lastname: Homann
authors.forename: Michael
authors.initials: M
authors.lastname: Duchrow
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Stanley K
authors.initials: SK
authors.lastname: Burt
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
mesh_terms: 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
chemical_list: D000706:Anaphylatoxins; D014408:Biomarkers, Tumor; D015926:Complement C3a