Abstract
Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary metabolic profiles in newly diagnosed colorectal cancer patients (stage I–IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (n = 16), pre-cachectic (n = 13), or non-cachectic (n = 23) based on standard criteria on weight loss over time at two time points. Urine samples were collected pre-surgery, and 6 and 12 months thereafter. Fat and muscle mass area were assessed utilizing computed tomography scans at the time of surgery. N = 152 compounds were detected using untargeted metabolomics with gas chromatography–mass spectrometry and n = 154 features with proton nuclear magnetic resonance spectroscopy. Thirty-four metabolites were overlapping across platforms. We calculated differences across groups and performed discriminant and overrepresentation enrichment analysis. We observed a trend for 32 compounds that were nominally significantly different across groups, although not statistically significant after adjustment for multiple testing. Nineteen compounds could be identified, including acetone, hydroquinone, and glycine. Comparing cachectic to non-cachectic patients, higher levels of metabolites such as acetone (Fold change (FC) = 3.17; p = 0.02) and arginine (FC = 0.33; p = 0.04) were observed. The two top pathways identified were glycerol phosphate shuttle metabolism and glycine and serine metabolism pathways. Larger subsequent studies are needed to replicate and validate these results.
Highlights
Cachexia is a multifactorial syndrome and affects 50–80% of all patients diagnosed with advanced cancer
We investigated the associations of urinary branched-chain amino acids (BCAAs) with parameters of energy balance and overall survival in colorectal cancer patients over time [17]
One-way ANOVA was used to compare mean differences across different phenotypes for continuous variables. 1 pValue : p-value for the comparison of mean concentrations across cachectic and non-cachectic patients; 2 pFDR : p-value from Benjamini–Hochberg procedure; 3 gas chromatography–mass spectrometry (GC–MS): Gas chromatography–mass spectrometry, 4 154 features with proton nuclear magnetic resonance (1 H-NMR): Proton nuclear magnetic resonance; 5 for 1 H-NMR values were not log transformed, we present log fold change values
Summary
Cachexia is a multifactorial syndrome and affects 50–80% of all patients diagnosed with advanced cancer. Depending on cancer type and stage, pre-cachexia is further characterized by systemic inflammation, low food intake, and poor response to cancer treatment. Cachectic cancer patients experience similar, but more-intense, symptoms compared to pre-cachectic cancer patients including severe weakness, fatigue, and loss of muscle strength [2]. Obese cancer patients with low muscle mass, a state known as sarcopenic obesity, suffer from increased treatment-related toxicity and higher mortality rates in comparison to patients not diagnosed with sarcopenic obesity [12]. The loss of muscle mass in sarcopenic patients is frequently masked by a high body mass index (BMI). Identifying these patients remains clinically challenging [12,13]
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