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Non-invasive prognostic protein biomarker signatures associated with colorectal cancer

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SURINOVA Silvia RADOVÁ Lenka CHOI Meena SROVNAL Josef BRENNER Hermann VITEK Olga HAJDUCH Marian AEBERSOLD Ruedi

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj EMBO MOLECULAR MEDICINE
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://embomolmed.embopress.org/content/embomm/7/9/1153.full.pdf
Doi http://dx.doi.org/10.15252/emmm.201404874
Obor Onkologie a hematologie
Klíčová slova colorectal cancer; prognostic protein biomarker; targeted proteomics
Přiložené soubory
Popis The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with comprehensive CRC characteristics. Clinical data included 8-year overall survival, tumor staging, histological grading, regional localization, and molecular tumor characteristics. The acquired quantitative proteomic dataset was subjected to the development of biomarker signatures predicting prognostic clinical endpoints. Protein candidates were selected into the signatures based on significance testing and a stepwise protein selection, each within 10-fold cross-validation. A six-protein biomarker signature of patient outcome could predict survival beyondclinical stage and was able to stratify patients into groups of better and worse prognosis. We further evaluated the performance of the signature on the mRNA level and assessed its prognostic value in the context of previously published transcriptional signatures. Additional signatures predicting regional tumor localization and disease dissemination were also identified. The integration ofrich clinical data, quantitative proteomic technologies, and tailored computational modeling facilitated the characterization of these signatures in patient circulation. These findings highlight the value ofa simultaneous assessment of important prognostic disease characteristics within a single measurement.

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