Serum metabonomics as a diagnostic approach for cancer-related fatigue

Abstract

In the present study, differences in metabolic pathways between patients with and without cancer-related fatigue (CRF) were examined to identify metabolic serum biomarkers of CRF. In this preliminary study, metabolic profiling was applied to analyze the serum samples from 14 patients with CRF and 11 non-CRF individuals (non-fatigue cancer survivors) by ultra-performance liquid chromatography coupled with mass spectrometry. Orthogonal partial least-squares discriminant analysis was adopted to evaluate the differences between the CRF and non-CRF groups. The CRF group was characterized by increases in phosphatidylethanolamine (PE; 18:0/0:0), LysoPE (0:0/20:4 and 0:0/16:0), lysophosphatidylcholine (LysoPC; 20:4, 22:4 and 16:0) and LysoPC/PC, phosphatidylserine (21:0/0:0), glycerophosphocholine and N-docosahexaenoyl γ-aminobutyric acid. Furthermore, decreases in anandamide, uric acid, dihydrouracil, LysoPE (0:0/22:5), 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, 19(R)-hydroxy-prostaglandin F1α, N-(3α,12α-dihydroxy-5β-cholan-24-oyl)-glycine, ketoleucine, indoxyl sulfate, α-N-phenylacetyl-L-glutamine and 1-linoleoyl-glycerophosphocholine were detected. These data indicate a possible disturbance in the metabolism of phospholipids and adjustments in the endocannabinoid system. The metabonomic approach may be helpful to determine the pathophysiological mechanisms of CRF and the identification of potential biomarkers for the accurate diagnosis of CRF. All clinical data were obtained from the 'Research on the efficacy of traditional Chinese medicine comprehensive intervention in cancer-related fatigue' (TCM-CRF) project. Medical Ethical Approval for TCM-CRF was approved by the Chinese Ethics Committee of Registering Clinical Trials. The approval number for the TCM-CRF study was ChiECRCT-2013038, and the TCM-CRF study was completed.

Keywords: UPLC/MS; cancer-related fatigue; diagnostic approach; metabolic profiling; serum.

Figure 1

Positive and negative ion base peak intensity (mAu) chromatograms of representative serum samples from a patient with CRF (WA) and a non-CRF (WB) subject. (A and B) Patient with CRF in (A) positive and (B) negative mode; (C and D) non-CRF in (C) positive and (D) negative mode. CRF, cancer-related fatigue; ESI, electron spray ionization; BPC, Base Peak Chromatogram; neg, negative; pos, positive; Frag, fragmentation.

Figure 2

Scores in (A) positive and (B) negative ion modes from the OPLS-DA model classifying ultra-performance liquid chromatography tandem mass spectrometry data in CRF (WA, green squares) and non-CRF (WB, blue squares) patients. Permutation test of the OPLS-DA model of WA and WB in (C) positive and (D) negative ion mode. The R2 (cum) and Q2 (cum) are the two parameters used to describe the goodness of the model at the minimum number of components cumulatively required (cum) to optimally give account of the data variability. OPLS-DA, orthogonal partial least-squares discriminant analysis; PC, principal component.

Figure 3

S-VIP plot in (A) positive and (B) negative ion modes from the OPLS-discriminant analysis model. The red squares represent the VIP-value plot. The black triangles represent the S-plot. OPLS, orthogonal partial least-squares; VIP, variable importance in the projection; p(corr), partial correlation coefficient; Corr.Coeffs, correlation coefficient.