Abstract 4787: Novel upfront sample enrichment nanotechnology identifies prostate, breast, colon, ovarian, lung, pancreatic, and melanoma cancer specific biomarker candidates
Authors: Claudia Fredolini, Davide Tamburro, Santosh Goud, Chandler King, Weidong Zhou, Paul Russo, Virginia Espina, Francesco Novelli, Devis Collura, Leonardo D'Urso, Claudio Belluco, Giovanni Muto, Enrico Garaci, Lance Liotta, Emanuel Petricoin, Alessandra Luchini
Journal: Cancer Research (2012)

Abstract BACKGROUND: Routine laboratory blood tests for biomarkers could dramatically simplify and improve cancer diagnosis, prognosis and tailored therapy. The tumor and its microenvironment, produce cascades of information that enrich the blood proteome with potential cancer biomarkers that could be highly informative about the establishment, progression and metastatic dissemination of cancer. Nevertheless, the identification of low abundance and labile cancer specific biomarkers in blood remains extremely challenging. Low abundance markers are masked by high abundance proteins such as albumin, and by non-specific markers whose changes accompany many diseases. In this study, we analyzed a large cohort of human serum samples from a wide-range of cancer conditions and benign states, and utilized a rapid and powerful nanoparticle-based biomarker capture technology. METHODS- We utilized isopropylacrylamide (NIPAm) core shell hydrogel particles, functionalized with two chemical baits, Cibacron blue F3GA and vinylsulfonic acid, for biomarker capture from 450 serum/plasma samples. Twenty age and stage-matched cancer and 20 to 40 benign/inflammatory controls were processed for each of the 7 cancer types, and proteins eluted from the particles were analyzed by high resolution LC-MS/MS analysis using an LTQ-Orbitrap (Thermo Fisher). All specimens were analyzed in a randomized, batch fashion, followed by an accurate comparison of the results in order to 1) identify a panel of biomarkers for each cancer type and distinguish protein which are involved in commons cancer mechanism and proteins which could uniquely indicate a particular cancer type and 2) avoid the technological bias that could be associated with the comparison of separated studies. RESULTS: For each cancer type we obtained a panel of hundreds of candidates biomarkers, a large number of them not previous identified by MS and/or never measured in plasma. Within the proteins identified are kinases, cytokines, growth factors, structural and nuclear proteins. Each panel of candidate biomarkers includes a) proteins unique for a cancer type, such as the tyrosine kinase Tec, specific for prostate cancer; b) proteins common to many cancer types such as, PRKAG2, CD9, Lipocalin 2, Annexin I, and SDFR-1 and c) numerous proteins whose role in cancer is novel or not well-described. CONCLUSIONS: Cancer-specific low abundance marker candidates have been identified using NanoTrap ™ nanoparticles, a novel rapid upfront sample processing biomarker capture technique. We are developing a protocol for the validation of the biomarkers based on MRM-MS. Further investigation will be required to understand the biological meaning and clinical value of the proteins identified. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4787. doi:1538-7445.AM2012-4787