Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and translational study

Abstract

BackgroundCachexia is a metabolic syndrome that affects up to 50–80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The ‘omics’ technologies provide a global view of biological systems. We hypothesize that blood‐based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge on its pathophysiology, and eventually postulate new therapeutic strategies.MethodsThis is a cross‐sectional observational study in two cohorts of cancer patients, with and without cachexia. Patients were consecutively recruited from routine clinical practice of a General Oncology Department at ‘12 de Octubre’ University Hospital. Selected clinical and biochemical features were collected. Blood metabolite fingerprinting was performed using three analytical platforms, gas chromatography coupled to mass spectrometry (GC–MS), capillary electrophoresis coupled to mass spectrometry (CE–MS), and liquid chromatography coupled to mass spectrometry (LC–MS). Besides, we performed pathway‐based metabolite analyses to obtain more information on biological functions.ResultsA total of 15 subjects were included in this study, 8 cachectic and 7 non‐cachectic patients. Metabolomic analyses were able to correctly classify their samples in 80% (GC–MS), 97% (CE–MS), 96% [LC–MS (positive mode)], and 89% [LC–MS (negative mode)] of the cases. The most prominent metabolic alteration in plasma of cachectic patients was the decrease of amino acids and derivatives [especially arginine, tryptophan, indolelactic acid, and threonine, with 0.4‐fold change (FC) compared with non‐cachectic patients], along with the reduction of glycerophospholipids [mainly lysophosphatidylcholines(O‐16:0) and lysophosphatidylcholines(20:3) sn‐1, FC = 0.1] and sphingolipids [SM(d30:0), FC = 0.5]. The metabolite with the highest increase was cortisol (FC = 1.6). Such alterations suggest a role of the following metabolic pathways in the pathophysiology of cancer cachexia: arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; lysine degradation; aminoacyl‐tRNA biosynthesis; fatty acid elongation in mitochondria; tricarboxylic acids cycle; among others.ConclusionsThese findings suggest that plasma amino acids and lipids profiling has great potential to find the mechanisms involved in the pathogenesis of cachexia. Metabolic profiling of plasma from cancer patients show differences between cachexia and non‐cachexia in amino acids and lipids that might be related to mechanisms involved in its pathophysiology. A better understanding of these mechanisms might identify novel therapeutic approaches to palliate this unmet medical condition.

Metabolic changes during respiratory syncytial virus infection of epithelial cells

“…The tool employed was the search engine CEU Mass Mediator (CMM) [35,36] that comprises 332,665 real compounds integrated from several metabolomics databases, including HMDB [37], METLIN [38], KEGG [39], and LIPID MAPS [40]. The annotation was based on (i) mass accuracy (maximum error mass was set on 20 ppm); (ii) retention time; (iii) possibility of cation and anion formation; and (iv) adduct formation [41].…”

1H-NMR Based Serum Metabolomics Identifies Different Profile between Sarcopenia and Cancer Cachexia in Ageing Walker 256 Tumour-Bearing Rats

“…The metabolic alterations in Wa group impacted mainly the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism pathways, clearly related to the higher tumour cells activities. Similarly, Cala and colleagues [6] observed that these same pathways were impacted in cancer cachectic patients. In accordance with our results, Quan Jun and colleagues [32] also found in a cancer cachexia experimental model metabolite perturbations related to muscle atrophy.…”

“…The elucidation of the molecular mechanisms of sarcopenia and cachexia is important to prevent the process of skeletal muscle atrophy and, consequently, improve the survival of cancer patients [4,5]. In this context, many studies have been interested in identifying circulating markers of muscle wasting process during cancer cachexia in clinical [6][7][8][9] and preclinical [10][11][12] models.…”

“…Metabolomics studies have revealed a distinct plasma, serum, and urine metabolic profile of cancer cachexia patients [6,7]. Additionally, Boguszewicz and colleagues [8] described serum metabolic alterations as a characteristic for malnutrition or cachexia that can already be detected at the beginning of the treatment of head and neck squamous cell carcinoma patients.…”

Plasma Metabolic Signature of Atherosclerosis Progression and Colchicine Treatment in Rabbits

“…Instrumental analysis. Sample treatment and analysis for all techniques were performed as described elsewhere [44][45][46][47] . All procedures and conditions are fully described in the Supplementary material.…”