Abstract
Colorectal cancer (CRC) is a high incidence disease, characterized by high morbidity and mortality rates. Early diagnosis remains challenging because fecal occult blood screening tests have performed sub-optimally, especially due to hemorrhoidal, inflammatory, and vascular diseases, while colonoscopy is invasive and requires a medical setting to be performed. The objective of the present study was to determine if serum metabolomic profiles could be used to develop a novel screening approach for colorectal cancer. Furthermore, the study evaluated the metabolic alterations associated with the disease. Untargeted serum metabolomic profiles were collected from 100 CRC subjects, 50 healthy controls, and 50 individuals with benign colorectal disease. Different machine learning models, as well as an ensemble model based on a voting scheme, were built to discern CRC patients from CTRLs. The ensemble model correctly classified all CRC and CTRL subjects (accuracy = 100%) using a random subset of the cohort as a test set. Relevant metabolites were examined in a metabolite-set enrichment analysis, revealing differences in patients and controls primarily associated with cell glucose metabolism. These results support a potential use of the metabolomic signature as a non-invasive screening tool for CRC. Moreover, metabolic pathway analysis can provide valuable information to enhance understanding of the pathophysiological mechanisms underlying cancer. Further studies with larger cohorts, including blind trials, could potentially validate the reported results.
Highlights
Colorectal cancer (CRC) represents approximately 10% of all annually diagnosed cancers and cancer-related deaths worldwide
Fifty of the 200 participants presented with no lesions and were considered healthy subjects (HS), 50 presented with benign colon or rectum tumors (BCRT), and 100 were diagnosed with CRC
We evaluated the diagnostic performance of a machine learning ensemble model based on the statistical comparison of the serum metabolomic fingerprints of individuals that are and are not affected by malignant colorectal cancer
Summary
Colorectal cancer (CRC) represents approximately 10% of all annually diagnosed cancers and cancer-related deaths worldwide. It is the second most frequent cancer diagnosed in women and the third most in men [1]. While screening programs and improved lifestyle habits help stabilize incidence in these countries, the global incidence is expected to increase as affluence increases and lifestyle changes in developing countries [2]. Both hereditary and environmental risk factors play a role in the onset of CRC. A subgroup of patients (3–5% of all CRC [4]) is affected by hereditary CRC syndrome, which can be subdivided into non-polyposis (such as Lynch syndrome) and polyposis syndromes, such as
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