Global serum metabolomics profiling of colorectal cancer (Review)

Abstract

Accurate diagnosis of colorectal cancer (CRC) relies on the use of invasive tools such as colonoscopy and sigmoidoscopy. Non-invasive tools are less sensitive in detecting the disease, particularly in the early stage. A number of researchers have used metabolomics analyses on serum/plasma samples of patients with CRC compared with normal healthy individuals in an effort to identify biomarkers for CRC. The aim of the present review is to compare reported serum metabolomics profiles of CRC and to identify common metabolites affected among these studies. A literature search was performed to include any experimental studies on global metabolomics profile of CRC using serum/plasma samples published up to March 2018. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used to assess the quality of the studies reviewed. In total, nine studies were included. The studies used various analytical platforms and were performed on different populations. A pathway enrichment analysis was performed using the data from all the studies under review. The most affected pathways identified were protein biosynthesis, urea cycle, ammonia recycling, alanine metabolism, glutathione metabolism and citric acid cycle. The metabolomics analysis revealed levels of metabolites of glycolysis, tricarboxylic acid cycle, anaerobic respiration, protein, lipid and glutathione metabolism were significantly different between cancer and control samples. Although the majority of differentiating metabolites identified were different in the different studies, there were several metabolites that were common. These metabolites include pyruvic acid, glucose, lactic acid, malic acid, fumaric acid, 3-hydroxybutyric acid, tryptophan, phenylalanine, tyrosine, creatinine and ornithine. The consistent dysregulation of these metabolites among the different studies suggest the possibility of common diagnostic biomarkers for CRC.

Association between Metabolites and the Risk of Lung Cancer: A Systematic Literature Review and Meta-Analysis of Observational Studies

“…Amino acids have been reported to be associated with other types of cancer in earlier reviews [ 88 , 89 , 90 , 91 ]. The amino acids identified in our meta-analyses (methionine, tryptophan and proline) were identified in previous reviews, although the direction of association is different for proline (i.e., positive association in our meta-analysis on lung cancer but inverse association for other cancer types) [ 88 , 90 , 91 ].…”

Integrating Two-Dimensional Gas and Liquid Chromatography-Mass Spectrometry for Untargeted Colorectal Cancer Metabolomics: A Proof-of-Principle Study

“…In the past several years, a number of global metabolomic studies on CRC have been published. These studies utilized diverse biological specimens, including blood (plasma/serum) as the most common type [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], followed by tissue [ 27 , 39 , 40 , 41 , 42 ], feces [ 39 , 40 , 43 ], and urine [ 44 , 45 ], while others aimed specifically to detect volatile metabolites in breath and in other types of biospecimens [ 21 , 46 ]. To our knowledge, only two of these were prospective studies where biospecimens were collected before cancer development [ 26 , 34 ], aiming to identify etiological pathways.…”

“…Blood is the most widely used clinical specimens. Hashim et al [ 23 ] recently reviewed the results of blood-based global metabolomic studies for CRC. The authors identified nine studies and found that the number of annotated metabolites in each study vastly varied from 14 [ 25 ] to 447 [ 34 ], not necessarily in a platform-dependent manner.…”

“…What was apparent in the aforementioned review and other recent papers on circulating CRC-associated metabolites is that very few metabolites have been detected consistently across the studies. Even if a metabolite was reported in more than one study, often the direction association was different [ 23 ]. For instance, there were no lipid metabolites commonly detected in the same direction in recent studies [ 26 , 28 , 29 ].…”

“…For instance, there were no lipid metabolites commonly detected in the same direction in recent studies [ 26 , 28 , 29 ]. The most consistently observed in the same direction as well as by more than one platform were pyruvic acid (up-regulated) and tryptophan (down-regulated) [ 23 ]. However, in our study population, neither pyruvic acid nor tryptophan showed significant abundance difference between the cases and the controls, being the fold changes of these metabolites close to unity (0.94–0.99, data not shown).…”