A new strategy for searching determinants in colorectal cancer progression through whole-part relationship combined with multi-omics.

Abstract: The high incidence and mortality of colorectal cancer (CRC) and the lack of adequate diagnostic molecules have led to poor treatment outcomes for colorectal cancer, making it particularly important to develop methods to obtain molecular with significant diagnostic effects. Here, we proposed a whole and part study strategy (early-stage colorectal cancer as "part" and colorectal cancer as "whole") to identify specific and co-pathways of change in early-stage and colorectal cancers and to discover the determinants of colorectal cancer development. Metabolite biomarkers discovered in plasma may not necessarily reflect the pathological status of tumor tissue. To explore the determinant biomarkers associated with plasma and tumor tissue in the CRC progression, multi-omics were performed on three phases of biomarker discovery studies (discovery, identification and validation) including 128 plasma metabolomes and 84 tissue transcriptomes. Importantly, we observe that the metabolic levels of oleic acid and FA (18:2) in patients with colorectal cancer were much higher than in healthy people. Finally, biofunctional verification confirmed that oleic acid and FA (18:2) can promote the growth of colorectal cancer tumor cells and be used as plasma biomarkers for early-stage colorectal cancer. We propose a novel research strategy to discover co-pathways and important biomarkers that may be targeted for a potential role in early colorectal cancer, and our work provides a promising tool for the clinical diagnosis of colorectal cancer. [Display omitted] • A "whole part" strategy based on multi-omics analysis is proposed. • Specific and co-pathways of change in ECRC and CRC were identified. • Oleic acid and FA18:2 promote the tumor genesis of ECRC in vivo. [ABSTRACT FROM AUTHOR]