title: Colorectal cancer biomarkers: to be or not to be? Cautionary tales from a road well travelled.
abstract: Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide and places a major economic burden on the global health care system. The time frame for development from premalignant to malignant disease typically spans 10-15 years, and this latent period provides an ideal opportunity for early detection and intervention to improve patient outcomes. Currently, early diagnosis of CRC is hampered by a lack of suitable non-invasive biomarkers that are clinically or economically acceptable for population-based screening. New blood-based protein biomarkers for early detection of CRC are therefore urgently required. The success of clinical biomarker discovery and validation studies is critically dependent on understanding and adjusting for potential experimental, analytical, and biological factors that can interfere with the robust interpretation of results. In this review we outline some important considerations for research groups undertaking biomarker research with exemplars from our studies. Implementation of experimental strategies to minimise the potential effects of these problems will facilitate the identification of panels of biomarkers with the sensitivity and specificity required for the development of successful tests for the early detection and surveillance of CRC.
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Kim Y C
authors.initials: KY
authors.lastname: Fung
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Edouard
authors.initials: E
authors.lastname: Nice
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Ilka
authors.initials: I
authors.lastname: Priebe
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Belobrajdic
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Aloke
authors.initials: A
authors.lastname: Phatak
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Leanne
authors.initials: L
authors.lastname: Purins
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Tabor
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Celine
authors.initials: C
authors.lastname: Pompeia
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Trevor
authors.initials: T
authors.lastname: Lockett
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Adams
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Antony
authors.initials: A
authors.lastname: Burgess
authors.affiliation: Kim YC Fung, Ilka Priebe, Damien Belobrajdic, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Leah Cosgrove, CSIRO, Preventative Health National Research Flagship, Adelaide, SA 5000, Australia.
authors.forename: Leah
authors.initials: L
authors.lastname: Cosgrove
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D055088:Early Detection of Cancer; D006801:Humans; D011237:Predictive Value of Tests; D011379:Prognosis; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D013048:Specimen Handling; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D011933:Reagent Kits, Diagnostic
keywords: Bias; Biomarker; Colorectal cancer; Diagnostic; Discovery; Validation