||5R01CA207371-05 Interpret this number
||University Of Utah
||Metabolomic Strategies for Discovery and Validation of Biomarkers of Colorectal Cancer Recurrence
Clinical decision making will increasingly depend on validated, high-quality biomarkers that can be used to
guide cancer surveillance and tailor appropriate treatment. Identifying colorectal cancer (CRC) markers is
particularly critical, as CRC is common in both men and women (8% of all incident USA cancers) and is
frequently lethal (USA 5-year survival rate: 65%). To date, clinically useful biomarkers predictive of recurrence
or survival for CRC patients are limited. Treatment decisions are based largely on clinical and pathologic
parameters, with little else to guide risk and treatment stratification of patients.
This study will focus on metabolite biomarker discovery and validation utilizing 1,840 patients (stage I-III)
with 6,004 repeat blood samples from the existing ColoCare Study, a multi-center prospective cohort of newly
diagnosed CRC patients, including detailed demographic, clinical, epidemiologic, and follow-up data, for which
blood samples are collected at multiple standardized time points, using identical protocols across study sites.
This diverse population ensures broad generalizability and clinical applicability of identified biomarkers. CRC is
known to affect metabolism, and thus it is anticipated that markers of altered metabolism should yield useful
diagnostic information. Our discovery of metabolic biomarkers will yield novel, distinct findings, and will also be
synergistic with ongoing, separate analyses of proteomic, glycomic, and autoantibody biomarkers in the
ColoCare Study patient population. This project’s specific aims are:
To use state-of-the art, well-validated metabolomic platforms to discover and verify novel biomarkers:
1. Predictive of recurrence among CRC patients: Using samples collected at diagnosis and follow-up, we
will identify metabolites predictive of risk of recurrence in stage I/II and stage III patients.
2. Capable of early detection of CRC recurrence: Using serial samples collected at regular post-surgical
intervals (6, 12, and 24 months), we will identify biomarkers useful for disease monitoring for recurrence.
Metabolite biomarkers will include >2,500 lipids and aqueous metabolites (MW<1,000; distinct from
proteins). We will evaluate the performance of identified markers separately for men and women and perform
analyses to understand factors that affect their performance.
Our long-term goal is to develop clinical-grade biomarker assays that have a significant impact on reducing
morbidity and mortality associated with CRC through guidance of treatment/follow-up decision making and
characterization of risk of recurrence. The proposed metabolomics platforms are state-of-the art, have yielded
potentially useful biomarkers in the past, and have not yet been used in the context of CRC prognosis. The
study uses a rigorous multi-step design and is expected to yield clinically robust markers ready for rapid