Blood-based protein biomarker panel for the detection of colorectal cancer
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 pr...
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| Published in | PloS one Vol. 10; no. 3; p. e0120425 |
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| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
20.03.2015
Public Library of Science (PLoS) |
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| Abstract | 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.
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).
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. |
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| AbstractList | 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.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).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. 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. 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. BACKGROUNDThe 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.PRINCIPAL FINDINGSIn 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).CONCLUSIONSDue 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. 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. Principal Findings 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. 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. Principal Findings 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. 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. 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). 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. |
| Audience | Academic |
| Author | Fung, Kim Y C Brierley, Gemma V Burgess, Antony Lockett, Trevor McMurrick, Paul Gibbs, Peter Tie, Jeanne Adams, Timothy E Pompeia, Celine Buckley, Michael J Priebe, Ilka K Cosgrove, Leah J Purins, Leanne Nice, Edouard Tabor, Bruce Moore, James Ruszkiewicz, Andrew |
| AuthorAffiliation | Deutsches Krebsforschungszentrum, GERMANY 3 Cabrini Hospital, Melbourne, Victoria, Australia 2 Royal Melbourne Hospital, Melbourne, Victoria, Australia 1 CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia 8 Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia 6 Monash University, Melbourne, Victoria, Australia 4 Royal Adelaide Hospital, Adelaide, South Australia, Australia 7 CSIRO Materials Science & Engineering, Parkville, Victoria, Australia 9 Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Victoria, Australia 5 SA Pathology, Adelaide, South Australia, Australia |
| AuthorAffiliation_xml | – name: 2 Royal Melbourne Hospital, Melbourne, Victoria, Australia – name: 4 Royal Adelaide Hospital, Adelaide, South Australia, Australia – name: 5 SA Pathology, Adelaide, South Australia, Australia – name: Deutsches Krebsforschungszentrum, GERMANY – name: 7 CSIRO Materials Science & Engineering, Parkville, Victoria, Australia – name: 3 Cabrini Hospital, Melbourne, Victoria, Australia – name: 6 Monash University, Melbourne, Victoria, Australia – name: 1 CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – name: 8 Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia – name: 9 Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Victoria, Australia |
| Author_xml | – sequence: 1 givenname: Kim Y C surname: Fung fullname: Fung, Kim Y C organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 2 givenname: Bruce surname: Tabor fullname: Tabor, Bruce organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 3 givenname: Michael J surname: Buckley fullname: Buckley, Michael J organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 4 givenname: Ilka K surname: Priebe fullname: Priebe, Ilka K organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 5 givenname: Leanne surname: Purins fullname: Purins, Leanne organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 6 givenname: Celine surname: Pompeia fullname: Pompeia, Celine organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 7 givenname: Gemma V surname: Brierley fullname: Brierley, Gemma V organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 8 givenname: Trevor surname: Lockett fullname: Lockett, Trevor organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia – sequence: 9 givenname: Peter surname: Gibbs fullname: Gibbs, Peter organization: Royal Melbourne Hospital, Melbourne, Victoria, Australia – sequence: 10 givenname: Jeanne surname: Tie fullname: Tie, Jeanne organization: Royal Melbourne Hospital, Melbourne, Victoria, Australia – sequence: 11 givenname: Paul surname: McMurrick fullname: McMurrick, Paul organization: Cabrini Hospital, Melbourne, Victoria, Australia – sequence: 12 givenname: James surname: Moore fullname: Moore, James organization: Royal Adelaide Hospital, Adelaide, South Australia, Australia – sequence: 13 givenname: Andrew surname: Ruszkiewicz fullname: Ruszkiewicz, Andrew organization: SA Pathology, Adelaide, South Australia, Australia – sequence: 14 givenname: Edouard surname: Nice fullname: Nice, Edouard organization: Monash University, Melbourne, Victoria, Australia – sequence: 15 givenname: Timothy E surname: Adams fullname: Adams, Timothy E organization: CSIRO Materials Science & Engineering, Parkville, Victoria, Australia – sequence: 16 givenname: Antony surname: Burgess fullname: Burgess, Antony organization: Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Victoria, Australia – sequence: 17 givenname: Leah J surname: Cosgrove fullname: Cosgrove, Leah J organization: CSIRO Preventative Health National Research Flagship, Adelaide, South Australia, Australia |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25793510$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2015 Public Library of Science 2015 Fung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2015 Fung et al 2015 Fung et al |
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| License | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. Creative Commons Attribution License |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: KYCF BT MJB TL AB EN LJC PG CP TEA. Performed the experiments: IKP LP GVB. Analyzed the data: KYCF BT MJB IKP LP GVB. Contributed reagents/materials/analysis tools: PG JT PMc JM AR EN LJC TEA. Wrote the paper: KYCF BT MJB IKP LP LJC EN TL CP AB TEA. |
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| Snippet | 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... Background The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second... BACKGROUNDThe majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second... Background The majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second... |
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| SubjectTerms | Adaptor Proteins, Signal Transducing Aged Aged, 80 and over Biomarkers Biomarkers, Tumor - blood Blood Blood tests Cancer Cancer diagnosis Carrier Proteins - blood Case-Control Studies Chemokines Clinical trials Colonoscopy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - blood Colorectal Neoplasms - pathology Deoxyribonucleic acid Diagnostic software Diagnostic systems DNA DNA methylation Feces Female Gastroenterology Gene expression Genetic testing Hospitals Humans Insulin Insulin-Like Growth Factor Binding Protein 2 - blood Insulin-like growth factor-binding protein 2 Intercellular Signaling Peptides and Proteins - blood Kinases Male Medical diagnosis Medical screening Membrane Proteins - blood Middle Aged Mortality Patients Polyps Population Protein binding Proteins Pyruvate kinase Pyruvic acid Risk analysis Risk factors Sensitivity Studies Systematic review Thyroid Hormone-Binding Proteins Thyroid Hormones - blood Tumors |
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| Title | Blood-based protein biomarker panel for the detection of colorectal cancer |
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