Colorectal cancer (CRC) is one of the most common tumors in developed countries. The five-year survival rate decreases depending on how advanced the CRC is when first diagnosed. Screening has been proven to greatly reduce mortality from colorectal cancer, but an ideal screening tool is far from being established. Here, we aimed to discover and validate early CRC biomarkers by means of an untargeted/targeted metabolomic approach. A preliminary untargeted analysis of plasma lipids performed on a small patient cohort (30 plasma samples) revealed some alterations that occurred in the presence of this tumor. In particular, medium-chain fatty acids with between six and twelve carbon atoms (C6–C12) were found to be the lipid class that showed the most marked changes upon the development of CRC. In order to evaluate the utility of this lipid class as diagnostic CRC biomarkers, a further study based on a wider cohort of patients (117 plasma samples) was performed. Using a targeted approach, these fatty acids were quantified in plasma samples by means of fast gas chromatography coupled to a time-of-flight analyzer. Plasma samples from patients with CRCs at different tumor stages were analyzed and compared to those from healthy subjects, ulcerative colitis patients, high-grade dysplasia adenoma patients, and breast cancer patients in order to test the specificity and sensitivity of these possible biomarkers. Results revealed significant differences among the considered groups in terms of their C6, C8, C10, and C12 fatty acid plasma concentrations. In particular, receiver operating characteristic (ROC) curves obtained for the C10 fatty acid gave an area under the curve of 0.8195 along with a sensitivity of 87.8 % and a specificity of 80 %, strongly suggesting that it could be a valuable early diagnostic biomarker of CRC.
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This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), “Progetto Regionale Speciale: Veneto 2010–2014,” and by funding from Ricerca Finalizzata of the Italian Healthcare Ministry (grant code number: RF-2011-02349645). The authors would like to thank U. Saini and M.S. Klee (DANI Instruments S.A.) for their support.
This study was conducted according to the principles expressed in the Declaration of Helsinki. All blood samples were collected under the full ethical approval of the ethics committee and only after informed consent had been obtained from all of the patients enrolled in the study.
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Crotti, S., Agnoletto, E., Cancemi, G. et al. Altered plasma levels of decanoic acid in colorectal cancer as a new diagnostic biomarker. Anal Bioanal Chem 408, 6321–6328 (2016). https://doi.org/10.1007/s00216-016-9743-1
- Colorectal cancer
- Free fatty acids