Plasma Biomarkers for Colorectal Cancer Diagnosis Based on Metabolomics

Abstract

Background: Metabolomics has been widely applied and has great potentialities in biomarkers identification for colorectal cancer (CRC). However, it turns out to be a hindrance by far for effective clinical translation owing to huge number and high inconsistency of biomarkers. Methods: We identified and verified differential plasma metabolites of CRC via a two-stage case-control metabolomics study in a population from Northeast China. Using receiver operating characteristic curve and pathway enrichment analyses, we selected biomarkers with favorable diagnostic efficiency and biological significance. We confirmed the tumor-specificity of these biomarkers by a metabolomics study of tumor-adjacent non-malignant paired tissue. Moreover, we conducted a systemic review of previous metabolomics studies in CRC to find biomarkers with external reproducibility in multiple populations. Results: We proposed three sets of candidate biomarkers of CRC with a particular focus on diagnostic efficiency, biological significance, tumor specificity, and external reproducibility. We showed that a five-biomarker panel of L-Tryptophan, 13-OxoODE, IDP, Glycochenodeoxycholate, and LysoPC(16:0) exhibited excellent diagnostic performance, favorable biological significance, and tumor specificity in our population. A six-biomarker panel of L−Phenylalanine, Linoleic acid, Citric acid, Inosine, Glycocholic acid, and LysoPC(14:0) showed the best extrapolation in diverse populations. Four metabolites (L-Tryptophan, Linoleic acid, Glycocholic acid, and LysoPC(16:0)) were ultimately recommended as the best combination with multiple advantages. Conclusion: We screened out the optimal panels of plasma biomarkers for CRC diagnosis and elucidated the potential usefulness of CRC metabolites under different requirements. Our proposed method may provide a powerful approach for metabolic biomarkers screening in other diseases. Funding Statement: This work was supported by grants from National Nature Science Foundation of China (81773503, 81573147, and 81473055), Scientific Research Foundation for the Returned Overseas Scholars of Heilongjiang Province (LC2018033), and Natural Science Foundation of Heilongjiang Province of China (for Youths, QC2018111). Declaration of Interests: All authors have declared that no conflict of interest exists. Ethics Approval Statement: We carried out this study after obtaining written informed consent from all the study subjects and approval from the Human Research and Ethics Committee of Harbin Medical University. All experiments including relevant details were performed in accordance with relevant guidelines and regulations.