High-Sensitivity Blood-Based Detection of Breast Cancer by Multi Photon Detection Diagnostic Proteomics

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• 作者：Andrzej K. Drukier ; Nathasha Ossetrova ; Elena Schors ; Galya Krasik ; Ivan Grigoriev ; Christina Koenig ; Miko Sulkowski ; Jerzy Holcman ; Larry R. Brown ; John E. Tomaszewski ; Mitchell D. Schnall ; Richard S
• 刊名：Journal of Proteome Research
• 出版年：2006
• 出版时间：August 2006
• 年：2006
• 卷：5
• 期：8
• 页码：1906 - 1915
• 全文大小：339K
• 年卷期：v.5,no.8(August 2006)
• ISSN：1535-3907

文摘

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 by200- to 1000-fold (1 femtogram/mL). This has allowed the measurement of cancer biomarkers withvery low concentrations in blood that could not be measured for full patient cohorts with conventionalimmunoassays. Sensitivity and specificity in cancer detection have been found to be potentiated byuse of immunoassay panels which include tissue-specific cancer biomarkers as well as cytokines andangiogenic factors. The ultrasensitive immunoassays revealed that patient to patient variations in theconcentrations of individual biomarkers in blood can extend over many orders of magnitude (up tosix) and that the distributions of biomarker concentrations over patient cohorts are non-Gaussian. Newmethods of data analysis which correlate abundances of multiple, different biomarkers have beendeveloped to deal with such data sets. Sensitivity and specificity of about 95% have been achieved forblood-based detection of breast cancer in pilot studies on 250 patients and 95 controls. Pilot studiesindicate that this methodology may also allow differentiation of malignant breast cancer from benignlesions and can provide similar sensitivity and specificity for other epithelial cancers such as prostatecancer, ovarian cancer and melanoma. The methods developed for selection, application, and evaluationof very high sensitivity biomarker panels are expected to have general relevance for diagnosticproteomics.