title: High-sensitivity blood-based detection of breast cancer by multi photon detection diagnostic proteomics.
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 1,000-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.
authors.affiliation: BioTraces Inc., 12455 Sunrise Valley Dr., Herndon, Virginia 20171, USA.
authors.forename: Andrzej K
authors.initials: AK
authors.lastname: Drukier
authors.forename: Nathasha
authors.initials: N
authors.lastname: Ossetrova
authors.forename: Elena
authors.initials: E
authors.lastname: Schors
authors.forename: Galya
authors.initials: G
authors.lastname: Krasik
authors.forename: Ivan
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Christina
authors.initials: C
authors.lastname: Koenig
authors.forename: Miko
authors.initials: M
authors.lastname: Sulkowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holcman
authors.forename: Larry R
authors.initials: LR
authors.lastname: Brown
authors.forename: John E
authors.initials: JE
authors.lastname: Tomaszewski
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Schnall
authors.forename: Richard
authors.initials: R
authors.lastname: Sainsbury
authors.forename: Anne E
authors.initials: AE
authors.lastname: Lokshin
authors.forename: Jasminka
authors.initials: J
authors.lastname: Godovac-Zimmermann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001769:Blood; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000175:diagnosis; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D017785:Photons; D017430:Prostate-Specific Antigen / Q000097:blood; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6; D016209:Interleukin-8; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D017430:Prostate-Specific Antigen