Metabolic profiling analysis for clinical urine of colorectal cancer

Abstract

Aim:To demonstrate the little-known metabolic changes and pathways in patients with colorectal cancer (CRC). Methods:We used gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) to perform metabolic profiling of urine samples from 163 consecutive patients with CRC and 111 healthy controls without history of gastrointestinal tumors. The metabolic profiles were assayed using multivariate statistical analysis and oneway analysis of variance, and further analyzed to identify potential marker metabolites related to CRC. The GC-TOF/MS-derived models showed clear discriminations in metabolic profiles between the CRC group and healthy control group. Results:We demonstrated that 15 metabolites contributed to the differences. Among them, eleven metabolites were significantly upregulated, while other four metabolites were downregulated in the urine samples of CRC patients compared with healthy controls. Pathway analysis revealed changes in energy metabolism of patients with CRC, which are reflected in the upregulation of glycolysis and amino acid metabolism and the downregulation of lipid metabolism. Our study revealed the metabolic profile of urine from CRC patients and indicated that GC-TOF/MS-based methods can distinguish CRC from healthy controls. Conclusion:GC-TOF/MS-based metabolomics has the potential to be developed into a novel, non-invasive, and painless clinical tool for CRC diagnosis, and may contribute to an improved understanding of disease mechanisms.

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

“…In our review, most studies employed a type of mass spectrometry analysis, with three studies employing 1 H-NMR analysis [29,42,53]. Liquid-Chromatography-Mass Spectrometry (LCMS), including Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), was the most popular method for analysis, with eighteen identified studies that applied this technique [22][23][24]26,30,31,33,35,36,38,39,41,43,[47][48][49][50]52], followed by Gas Chromatography-Mass Spectrometry, which was conducted in seventeen studies [24,25,27,28,34,38,39,[44][45][46][48][49][50][51]54,56,57] (Figure 2b). These counts include four studies conducting both LCMS and GCMS.…”

“…Other methods of analysis included direct infusion mass spectrometry (1 study) [32], Capillary electrophoresis-time of flight mass spectrometry (CE-TOFMS) (3 studies) [37,40,55], and Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry (MALDI-TOF MS) (1 study) [58] (Figure 2b). Thirty studies [23][24][25][27][28][29][30][31][32][34][35][36][37][38][39][40][42][43][44][45][46][48][49][50]53,54,[56][57][58] employed untargeted metabolomic profiling, while 9 studies employed targeted metabolomics, either with a metabolite subset in mind to begin the study or as part of a validation of their untargeted data [22,25,26,28,35,47,51,52,55]. Of studies where the selections of analytical columns could be identified, 16 used a column that could identify polar and nonpolar compounds …”

“…Thirty studies [23][24][25][27][28][29][30][31][32][34][35][36][37][38][39][40][42][43][44][45][46][48][49][50]53,54,[56][57][58] employed untargeted metabolomic profiling, while 9 studies employed targeted metabolomics, either with a metabolite subset in mind to begin the study or as part of a validation of their untargeted data [22,25,26,28,35,47,51,52,55]. Of studies where the selections of analytical columns could be identified, 16 used a column that could identify polar and nonpolar compounds [22,[25][26][27][28]31,33,36,38,…”

“…Among these studies, Kim et 3b) [33,55,58]. Sensitivity values ranged from 0.72 to 1.0, while specificity values ranged from 0.733 to 1.0 [27,33,54,55,58]. Average sensitivity and specificity of diagnostic models reporting these values were 0.855 and 0.839, respectively.…”

“…Most studies employed a case-control research design, using either a healthy (carcinoma-free) control, adenomatous polyp group, or both. Twenty-one studies compared CRC directly to healthy control [24][25][26]31,33,36,38,39,[42][43][44][45][46][48][49][50][51][52][53][54]56]. Jing et al and Gao et al, conversely, compared CRC patients to an adenomatous polyp control [32,55] while eleven studies utilized CRC, healthy control, and adenomatous polyp groups [28][29][30]34,35,37,40,41,47,57,58].…”