CONTEXT: Cancer-related fatigue syndrome (CRFS) affects a significant minority of women successfully treated for breast cancer, with symptoms lasting up to several years after finishing therapy. OBJECTIVES: This analysis was conducted to identify plasma proteins associated with CRFS in disease-free breast cancer patients. METHODS: Women were divided into those meeting the CRFS criteria (cases) and a control group on the basis of a diagnostic interview. Plasma samples were collected from 45 cases and 45 controls. Proteomic analysis was conducted using surface-enhanced laser desorption/ionization, a mass spectrometry (MS) technique. This was followed by further sample processing using one-dimensional gels and trypsin digest for protein identification using liquid chromatography and database searching. RESULTS: CRFS was associated with a statistically significant increase in the intensity of seven MS spectra. A subsequent search of proteins corresponding to the MS spectra identified four acute phase proteins associated with a nonspecific immune response (serum amyloid A, collectin, and subunits of immunoglobulin G and complement C1Q). CONCLUSION: These novel results (using a technique not previously used in fatigue research) add further weight to the hypothesis that CRFS may be precipitated and prolonged by a nonspecific sustained inflammatory response. Importantly, this has been identified from a global analysis of plasma, which was conducted with no prior assumptions. Although these results need confirmation, we would suggest that future treatments for CRFS should consider focusing on the modulation of this presumed prolonged immune response.
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