Abstract
Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality in patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon reported weight loss. The ‘omics’ technologies allow us the opportunity to study the end points of many biological processes. Among these, blood-based metabolomics is a promising method to investigate the pathophysiology of human cancer cachexia and identify candidate biomarkers. In this study, we performed liquid chromatography mass spectrometry (LC/MS)-based metabolomics to investigate the metabolic profile of cancer-associated weight loss. Non-selected patients undergoing surgery with curative intent for upper gastrointestinal cancer were recruited. Fasting plasma samples were taken at induction of anaesthesia. LC/MS analysis showed that 6 metabolites were highly discriminative of weight loss. Specifically, a combination profile of LysoPC 18.2, L-Proline, Hexadecanoic acid, Octadecanoic acid, Phenylalanine and LysoPC 16:1 showed close correlation for eight weight-losing samples (≥5% weight loss) and nine weight-stable samples (<5%weight loss) between predicted and actual weight change (r = 0.976, p = 0.0014). Overall, 40 metabolites were associated with ≥5% weight loss. This study provides biological validation of the consensus definition of cancer cachexia (Fearon et al.) and provides feasible candidate markers for further investigation in early diagnosis and the assessment of therapeutic intervention.
Highlights
Cancer cachexia has been defined as “a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment” [1]
Building upon the theory that metabolites produced from tissue breakdown are likely to be found in plasma, we investigated whether we could use liquid chromatography mass spectrometry (LC/MS)-metabolomics to detect plasma metabolites associated with weight loss in upper GI cancer patients
Plasma samples were analysed from upper GI cancer patients (n = 18) taken from a cross-sectional cohort of upper GI cancer patients who were recruited to two previously-published studies of muscle transcriptomics (n = 65 pre-surgical rectus abdominis biopsies, and n = 12 pre- and post-surgical resection muscle biopsies) [12,13]
Summary
Cancer cachexia has been defined as “a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment” [1]. Cancer cachexia is characterized by loss of adipose tissue, skeletal muscle, and appetite, and impacts negatively the quality of life of patients with cancer, response to treatment and survival [2]. Potential markers of cachexia may have value through future studies as outcome measures of therapeutic intervention. Imaging methods such as CT and MRI are currently considered precise measures of body composition but have several limitations, including cost, availability, and exposure to radiation (in the case of CT) [3]
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