Metabolomics Analysis in Serum from Patients with Colorectal Polyp and Colorectal Cancer by ¹H-NMR Spectrometry

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Colorectal adenomatous polyps are at high risk for the development of CRC. In this report, we described the metabolic changes in the sera from patients with colorectal polyps and CRC by using the NMR-based metabolomics. 110 serum samples were collected from patients and healthy controls, including 40 CRC patients, 32 colorectal polyp patients, and 38 healthy controls. The metabolic profiles and differential metabolites of sera were analyzed by multivariate statistical analysis (MSA), including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. A total of 23 differential metabolites were identified from MSA. According to the pathway analysis and multivariate ROC curve-based exploratory analysis by using the relative concentrations of differential metabolites, we found abnormal metabolic pathways and potential biomarkers involved with the colorectal polyp and CRC. The results showed that the pyruvate metabolism and glycerolipid metabolism were activated in colorectal polyps. And the glycolysis and glycine, serine, and threonine metabolism were activated in CRC. The changed metabolism may promote cellular proliferation. In addition, we found that the rates of acetate/glycerol and lactate/citrate could be the potential biomarkers in colorectal polyp and CRC, respectively. The application of 1H-NMR metabolomics analysis in serum has interesting potential as a new detection and diagnostic tool for early diagnosis of CRC.

Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage

“…The AUC values were 0.96 (95% confidence interval, CI 0.91–1.00), 0.96 (95% confidence interval, CI 0.92–1.00), and 0.95 (95% confidence interval, CI 0.90–1.00), for PLS, RF, and SVM, respectively. Notably, creatinine [ 7 , 8 ], taurine [ 20 ], lactate [ 8 , 21 ], glutamate [ 19 ], CDP-choline [ 20 ], and glycerol-3-phosphate [ 22 ] have been previously reported as correlated to colon cancer from the analysis of urine, serum, or plasma samples from colon cancer patients.…”

“…The results suggested separate mechanisms of tumorigenesis for RCC and LCC. In addition, plasma metabolomics analysis from RCC and LCC in CRC patients recently reported six potential biomarkers (anserine, trimethylamine N-oxide, arginine, gamma-glutamyl-gamma-aminobutyraldehyde, indoxyl sulfate, and pyridoxal 5′-phosphate), however these, again, suffer from the issue of plasma biomarker discovery and subsequent validation [ 19 ].…”

The Role of Circulating CD16+CD56+ Natural Killer Cells in the Screening, Diagnosis, and Staging of Colorectal Cancer before Initial Treatment

“…One category of circulating biomarkers for CRC falls within the scope of gene regulation (microRNA or methylation) [31, 32]. Another category resides in serum metabolomics analysis [33]. In this sense, the circulating CD16+CD56+ NK cells have a predictive role in both screening and staging before surgical procedures.…”

A Novel Network Modelling for Metabolite Set Analysis: A Case Study on CRC Metabolomics

“…As the betweenness of these pathways is relatively large, they may play an important role in information flow in the network, which implies they may have a greater impact on the entire network when they are perturbed. For example, pyruvate metabolism (PI-26) is found in the polyp and cancer groups, which suggests that pyruvate metabolism acts as the core central pathway for MSAN network in abnormal states (polyps and cancer states) [34]. Interestingly, tyrosine metabolism (PI-18) is found to be a pivotal pathway in the healthy and cancer groups, but its betweenness in the polyp group prior to cancer development is much smaller.…”

“…(PI-19), alanine, aspartate and glutamate metabolism (PI-10), and inositol phosphate metabolism (PI-24). These pathways have been previously identified as targets or reported to be perturbed by colon cancer [34,35].…”