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High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics

High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics
High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics
We have developed several new methods for blood-based cancer detection by diagnostic proteomics. Ultrasensitive methods of immunoassay using multiphoton-detection (IA/MPD) increase sensitivity by 200- to 1000-fold (1 femtogram/mL). This has allowed the measurement of cancer biomarkers with very low concentrations in blood that could not be measured for full patient cohorts with conventional immunoassays. Sensitivity and specificity in cancer detection have been found to be potentiated by use of immunoassay panels which include tissue-specific cancer biomarkers as well as cytokines and angiogenic factors. The ultrasensitive immunoassays revealed that patient to patient variations in the concentrations of individual biomarkers in blood can extend over many orders of magnitude (up to six) and that the distributions of biomarker concentrations over patient cohorts are non-Gaussian. New methods of data analysis which correlate abundances of multiple, different biomarkers have been developed to deal with such data sets. Sensitivity and specificity of about 95% have been achieved for blood-based detection of breast cancer in pilot studies on 250 patients and 95 controls. Pilot studies indicate that this methodology may also allow differentiation of malignant breast cancer from benign lesions and can provide similar sensitivity and specificity for other epithelial cancers such as prostate cancer, ovarian cancer and melanoma. The methods developed for selection, application, and evaluation of very high sensitivity biomarker panels are expected to have general relevance for diagnostic proteomics.
breast cancer, proteomics, immunoassay, blood biomarkers, multiphoton detection
1535-3893
1906-1915
Drukier, Andrzej K.
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Ossetrova, Nathasha
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Schors, Elena
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Krasik, Galya
43da861e-d4ee-406e-8b75-c5a5bdf6c9e8
Grigoriev, Ivan
486cf916-32bd-4047-9080-66b5caf1c2af
Koenig, Christina
77f82258-7521-4025-bce5-e00122f6aff3
Sulkowski, Miko
85a906cc-c004-445c-9206-7361974a32a6
Holcman, Jerzy
cc92da70-eb7e-4aae-9bf2-c4397a9b3793
Brown, Larry R.
4ad19fda-dcef-41af-8e87-8defaf78f37f
Tomaszewski, John E.
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Schnall, Mitchell D.
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Sainsbury, Richard
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Lokshin, Anne E.
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Godovac-Zimmermann, Jasminka
d93345b7-7821-49a8-87cb-86a775ec3a21
Drukier, Andrzej K.
929255eb-c2bc-43a6-8242-47070a878f87
Ossetrova, Nathasha
5e59cc4c-ac4b-4e86-8b28-9ef575699ec6
Schors, Elena
3471122a-1560-40b9-962a-e14073e188c5
Krasik, Galya
43da861e-d4ee-406e-8b75-c5a5bdf6c9e8
Grigoriev, Ivan
486cf916-32bd-4047-9080-66b5caf1c2af
Koenig, Christina
77f82258-7521-4025-bce5-e00122f6aff3
Sulkowski, Miko
85a906cc-c004-445c-9206-7361974a32a6
Holcman, Jerzy
cc92da70-eb7e-4aae-9bf2-c4397a9b3793
Brown, Larry R.
4ad19fda-dcef-41af-8e87-8defaf78f37f
Tomaszewski, John E.
3718474f-704f-4d70-bd68-a0416e70249d
Schnall, Mitchell D.
ae424bed-a204-4216-b57b-544e6ae20263
Sainsbury, Richard
b7f51d64-83d0-4a44-a9cb-059fe5b5bcbc
Lokshin, Anne E.
e1000175-14a3-4379-b633-adec8dedb6c5
Godovac-Zimmermann, Jasminka
d93345b7-7821-49a8-87cb-86a775ec3a21

Drukier, Andrzej K., Ossetrova, Nathasha, Schors, Elena, Krasik, Galya, Grigoriev, Ivan, Koenig, Christina, Sulkowski, Miko, Holcman, Jerzy, Brown, Larry R., Tomaszewski, John E., Schnall, Mitchell D., Sainsbury, Richard, Lokshin, Anne E. and Godovac-Zimmermann, Jasminka (2006) High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics. Journal of Proteome Research, 5 (8), 1906-1915. (doi:10.1021/pr0600834).

Record type: Article

Abstract

We have developed several new methods for blood-based cancer detection by diagnostic proteomics. Ultrasensitive methods of immunoassay using multiphoton-detection (IA/MPD) increase sensitivity by 200- to 1000-fold (1 femtogram/mL). This has allowed the measurement of cancer biomarkers with very low concentrations in blood that could not be measured for full patient cohorts with conventional immunoassays. Sensitivity and specificity in cancer detection have been found to be potentiated by use of immunoassay panels which include tissue-specific cancer biomarkers as well as cytokines and angiogenic factors. The ultrasensitive immunoassays revealed that patient to patient variations in the concentrations of individual biomarkers in blood can extend over many orders of magnitude (up to six) and that the distributions of biomarker concentrations over patient cohorts are non-Gaussian. New methods of data analysis which correlate abundances of multiple, different biomarkers have been developed to deal with such data sets. Sensitivity and specificity of about 95% have been achieved for blood-based detection of breast cancer in pilot studies on 250 patients and 95 controls. Pilot studies indicate that this methodology may also allow differentiation of malignant breast cancer from benign lesions and can provide similar sensitivity and specificity for other epithelial cancers such as prostate cancer, ovarian cancer and melanoma. The methods developed for selection, application, and evaluation of very high sensitivity biomarker panels are expected to have general relevance for diagnostic proteomics.

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More information

Submitted date: 8 March 2006
Published date: August 2006
Keywords: breast cancer, proteomics, immunoassay, blood biomarkers, multiphoton detection

Identifiers

Local EPrints ID: 49219
URI: http://eprints.soton.ac.uk/id/eprint/49219
ISSN: 1535-3893
PURE UUID: febd26e0-b2b9-4667-905b-966ef691efac

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Date deposited: 25 Oct 2007
Last modified: 13 Mar 2019 20:54

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Contributors

Author: Andrzej K. Drukier
Author: Nathasha Ossetrova
Author: Elena Schors
Author: Galya Krasik
Author: Ivan Grigoriev
Author: Christina Koenig
Author: Miko Sulkowski
Author: Jerzy Holcman
Author: Larry R. Brown
Author: John E. Tomaszewski
Author: Mitchell D. Schnall
Author: Richard Sainsbury
Author: Anne E. Lokshin
Author: Jasminka Godovac-Zimmermann

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