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World J Gastroenterol. Jan 28, 2014; 20(4): 888-898
Published online Jan 28, 2014. doi: 10.3748/wjg.v20.i4.888
Colorectal cancer biomarkers: To be or not to be? Cautionary tales from a road well travelled
Kim YC Fung, Edouard Nice, Ilka Priebe, Damien Belobrajdic, Aloke Phatak, Leanne Purins, Bruce Tabor, Celine Pompeia, Trevor Lockett, Timothy E Adams, Antony Burgess, Leah Cosgrove
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
Edouard Nice, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3168, Australia
Aloke Phatak, CSIRO, Computational Informatics, Floreat, WA 6014, Australia
Timothy E Adams, CSIRO, Materials Science and Engineering, Parkville, VIC 3052, Australia
Antony Burgess, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
Author contributions: Fung KYC and Nice E wrote the paper; Priebe I performed the research and analysed the data; Fung KYC, Nice E and Priebe I contributed equally to the work; Belobrajdic D contributed data to the study; Fung KYC, Phatak A, Purins L, Tabor B and Pompeia C analysed the data; Lockett T, Adams TE, Burgess A and Cosgrove L designed the research.
Supported by The CSIRO Preventative Health National Research Flagship and the National Health and Medical Research Council, No. 1017078
Correspondence to: Kim YC Fung, PhD, CSIRO, Preventative Health National Research Flagship, PO Box 10041, Adelaide, SA 5000, Australia. kim.fung@csiro.au
Telephone: +61-8-83038840 Fax: +61-8-83038899
Received: September 26, 2013
Revised: November 26, 2013
Accepted: January 6, 2014
Published online: January 28, 2014
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.

Keywords: Biomarker, Bias, Colorectal cancer, Diagnostic, Discovery, Validation

Core tip: The identification of sensitive and specific biomarkers for the early diagnosis and surveillance of colorectal cancer is recognised as being fundamental to improve survival for this disease. Studies involving analyses of multiple biomarkers require consideration of many potential confounding issues, some of which are impossible or difficult to control for. Implementation of strategies which can overcome and account for potentially confounding variables is essential to ensure robust verification and validation of potential biomarkers and their successful evaluation in large and meaningful clinical cohorts that are representative of the target population, ultimately with successful translation into the clinic.