title: Blood-based protein biomarker panel for the detection of colorectal cancer.
abstract: BACKGROUND
  The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second most common internal cancer in Australia, only 30 per cent of the population considered to have risk factors participate in stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase screening compliance. A number of potential diagnostic blood-based protein biomarkers for CRC have been reported, but all lack sensitivity or specificity for use as a stand-alone diagnostic. The aim of this study was to identify and validate a panel of protein-based biomarkers in independent cohorts that could be translated to a reliable, non-invasive blood-based screening test.
  
  
  RESULTS
  In two independent cohorts (n = 145 and n = 197), we evaluated seven single biomarkers in serum of CRC patients and age/gender matched controls that showed a significant difference between controls and CRC, but individually lack the sensitivity for diagnostic application. Using logistic regression strategies, we identified a panel of three biomarkers that discriminated between controls and CRC with 73% sensitivity at 95% specificity, when applied to either of the two cohorts. This panel comprised of Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2).
  
  
  CONCLUSIONS
  Due to the heterogeneous nature of CRC, a single biomarker is unlikely to have sufficient sensitivity or specificity for use as a stand-alone diagnostic screening test and a panel of markers may be more effective. We have identified a 3 biomarker panel that has higher sensitivity and specificity for early stage (Stage I and -II) disease than the faecal occult blood test, raising the possibility for its use as a non-invasive blood diagnostic or screening test.
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Kim Y C
authors: KY
authors: Fung
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Bruce
authors: B
authors: Tabor
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Michael J
authors: MJ
authors: Buckley
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Ilka K
authors: IK
authors: Priebe
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Leanne
authors: L
authors: Purins
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Celine
authors: C
authors: Pompeia
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Gemma V
authors: GV
authors: Brierley
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Trevor
authors: T
authors: Lockett
authors: Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Peter
authors: P
authors: Gibbs
authors: Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Jeanne
authors: J
authors: Tie
authors: Cabrini Hospital, Melbourne, Victoria, Australia.
authors: Paul
authors: P
authors: McMurrick
authors: Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors: James
authors: J
authors: Moore
authors: SA Pathology, Adelaide, South Australia, Australia.
authors: Andrew
authors: A
authors: Ruszkiewicz
authors: Monash University, Melbourne, Victoria, Australia.
authors: Edouard
authors: E
authors: Nice
authors: CSIRO Materials Science & Engineering, Parkville, Victoria, Australia.
authors: Timothy E
authors: TE
authors: Adams
authors: Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Victoria, Australia.
authors: Antony
authors: A
authors: Burgess
authors: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia.
authors: Leah J
authors: LJ
authors: Cosgrove
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D018925:Chemokines; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D013963:Thyroid Hormones / Q000097:blood; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018925:Chemokines; D018971:Insulin-Like Growth Factor Binding Protein 2; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C498624:DKK3 protein, human; C577903:IGFBP2 protein, human