Cancer cachexia (CC) is a frequent unmet medical need. CC affects up to 80% of cancer patients, and it is indirectly responsible for at least 20% of cancer deaths. 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, definite diagnostic criteria of cachexia are lacking. The 'omics' technologies provide a global view of biological systems. Among these, blood-based metabolomics is a promising method for cachexia study.
This study is part of a pilot, observational, cross-sectional, case-control, hypothesis generating, IRB-reviewed, research project. Objective: discovery and selection of biomarkers of cancer cachexia. Anthropometric, clinical and biochemical data from consenting eligible cancer patients were collected. Plasma proteome was assessed by 2D gel electrophoresis and MALDITOF mass spectrometry. Metabolomics was evaluated by means of a multiplatform non-targeted approach of plasma samples (LC –MS, GC-MS and CE-MS), to increase metabolite coverage. Data were analysed by univariate and multivariate methods, using principal component analyses and error adjustments for multiple comparisons.
from metabolomics study are shown. Subjects: 15 cancer (ca) patients (pts), distributed as follows: Cachexia (CX): 8 pts (male:female 7:1; pancreatic ca: 3, melanoma: 3, biliary duct ca: 2); control (CN): 7 pts (M:F 6:1; colon ca: 1, esophageal ca: 1, gastric ca: 2, pancreatic ca: 1, melanoma: 1, sarcoma:1). Median age: CX 62 y (36-81), CN 64 y (48-80); median body mass index: CX 20 Kg/m2 (17-27), CN 25 Kg/m2 (21-27); median albumin: CX 3.4 mg/dL (2.1-4.1), CN 3.9 mg/dL (3.5-4.8). A total of 89 metabolites (Mbl) were significantly altered in CX pts. The Mbl with highest increase was cortisol (fold change 1.67, p = 0.03). The largest affected group of Mbl was 'amino acids and derivatives', all decreased. Glycerophospholipids, sphingolipids, steroid derivatives, fatty acids, aldehydes, phenylacetamides, carboxilic acids and derivatives, and indoles were also decreased.
These finding suggest that plasma amino acids and lipids profiling has great potential for improving cachexia cancer screening and diagnosis, and understanding disease pathogenesis. Of note, the increased values of cortisol should lead us to revisit the use of glucocorticoids in this setting. Substitutive therapy for some of the observed deficiencies might deserve clinical exploration.
Clinical trial identification
Legal entity responsible for the study
Instituto de Investigación Sanitaria Hospital 12 de Octubre
ISCIII-FEDER (PI10/2072) and Fundacion Mutua Madrileña.
All authors have declared no conflicts of interest.