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Early Detection of Cancer Biomarkers at the Highest Level of Confidence Using Exhaled Breath: Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Biosensors Designed by Nature

Touradj Solouki, Michael F. McCulloch, James C. Walker, and Unyime O. Nseyo

The following paper was presented at "The Emerging Role of Screening and Prevention in Women's Cancers," May 4th and 5th, 2006, at the New York University School Of Medicine sponsored by the Lynne Cohen Foundation. Click here to download our detailed project display.

Early detection of any cancer disease is one of the most important factors contributing to patient survival. For example, while the 5-year survival rates in women diagnosed with localized ovarian epithelial cancer is 94%, only 19% of women have their disease detected at this stage. 5-year survival decreases to 69% with regional metastasis and 29% with distant metastasis. Hence early diagnosis is critical. However, tests currently in use for diagnosis of ovarian cancer, serum marker CA 125, transvaginal ultrasound, and pelvic examinations, have both high false-negative and false positive rates. False negatives would fail to find disease early, and false-positives may lead to anxiety and invasive diagnostic tests and unnecessary oophorectomies.

With breast cancer, 5-year survival for localized disease is 98%. This decreases to 80% with regional metastasis and 26% with distant metastasis. However, false-positive rates of mammographic screening for breast cancer can reach 15%, leading to patient distress and additional costs of care. Every $100 spent for mammographic screening incurs an estimated $33 to evaluate false-positive results. As many as 50% of women will have at least one false-positive mammogram in a 10 year period of screening, and a 20% chance of a false-positive leading to unnecessary biopsy. False-negative results are most likely in women with dense fibrous breast tissue or whose fast-growing cancers become symptomatic between screening intervals.

These problems can be greatly lessened through an innovative method, the chemical sensing/identification of biomarkers in exhaled breath condensate (EBC). Both trained dogs and conventional gas chromatography mass spectrometry (GC/MS) can distinguish breast cancer patients from controls using breath samples. However, the confident identification of unknown biomarkers with a GC/MS requires detectors with high sensitivity, mass resolving power, and mass measurement accuracy. A novel preconcentrator gas chromatography Fourier transform Ion Cyclotron Resonance Mass Spectrometer (PC/GC/FT-ICR MS) coupled with a cryofocuser inlet has been constructed in Dr. Solouki's laboratories to specifically address the above mentioned issues.

With the financial support (~ $750,000) from the Defense Advanced Research Projects Agency (DARPA), Dr. Solouki's team at the University of Maine has developed the first state-of-the-art PC/GC FT-ICR MS to acquire "sampleprints" and identify human exhaled breath (HEB) biomarkers for early detection of human diseases. Currently, this high performance GC/FT-ICR coupled with a sample "cryofocuser" is the only system of its kind worldwide and ideal for "fingerprinting" complex sample mixtures at the highest level of confidence. With additional financial support from the National Science Foundation (NSF), the PC/GC/FT-ICR MS capabilities were enhanced to establish a "Gold Standard" protocol to evaluate analytical performances of conventional sensors. The PC/GC/FT-ICR MS research has allowed the scientists in Maine to enhance detection limits, beat the GC/MS world record for ultrahigh mass resolving power by an order of magnitude, and identify unique biomarkers for bacterial differentiation. The unmatched analyte specificity offered by the multidimensional PC/GC/FT-ICR MS combined with the in-house developed trainable software packages such as Mass Identification Smart Tool (MIST) reduces/eliminates chemical misidentifications and is ideal for biomarker identification.

In this talk, advantages of these cutting-edge technologies in conjunction with the use of biological sensors, such as dogs, to advance cancer research and biomarker identification for noninvasive/early detection and screening of women cancers will be presented. A collaborative team of investigators from University of Maine, Florida State University, and Pine Street Foundation is seeking to understand precisely what compounds the dogs are smelling, and to then use that information to develop an "electronic nose" that can help in accurate, non-invasive early diagnosis.

Citation: Solouki T, McCulloch MF, Walker JC, Nseyo NO. Early detection of cancer biomarkers at the highest level of confidence using exhaled breath: Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and biosensors designed by nature.

Touradj Solouki: University of Maine, Orono ME 04469
Michael F. McCulloch: Pine Street Foundation, San Anselmo, CA 94960
James C. Walker: Florida State University, Tallahassee FL 32310
Unyime O. Nseyo: NF/SG Veterans Health System, Gainesville, FL 32601

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