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. 2014 Sep 24;9(9):e108132.
doi: 10.1371/journal.pone.0108132. eCollection 2014.

Serum complement C3f and fibrinopeptide A are potential novel diagnostic biomarkers for non-alcoholic fatty liver disease: a study in Qingdao Twins

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Serum complement C3f and fibrinopeptide A are potential novel diagnostic biomarkers for non-alcoholic fatty liver disease: a study in Qingdao Twins

Yong-Ning Xin et al. PLoS One. .

Abstract

Aims: To compare the different serum peptidome patterns between twins with and without non-alcoholic fatty liver disease (NAFLD) in order to help understand the pathogenesis of NAFLD and to identify potential diagnostic and therapeutic targets.

Methods: The peptidomics patterns of 63 cases with NAFLD were compared with their twin healthy controls in Qingdao, China. Peptides between 800 Da and 3,500 Da were captured and concentrated using C18 reversed-phase columns, followed by MALDI-TOF mass spectrometry. The sequences of peptides associated with NAFLD were further identified by MALDI-TOF-TOF. Further validation studies were conducted. One hundred additional serum samples were detected by commercially available ELISA kits to calculate the concentrations of complement C3f and fibrinopeptide A, respectively. The differences of these two peptides in the NAFLD and control groups were compared using SPSS 17.0, respectively.

Results: Compared with healthy controls, eleven peaks (861.1, 877.07, 904.5, 1206.57, 1350.64, 1518.7, 1690.9, 1777.94, 2931.29, 3190.4, 3261.4) were up-regulated and 7 peaks (942.44, 1020.47, 1060.06, 1211.7, 1263.63, 1449.76, 2768.3) were down-regulated in the NAFLD group. Two peptides derived from complement C3f and fibrinopeptide A, respectively, had the highest ROC values indistinguishing NAFLD cases from their normal controls. In the validation group, the concentrations of complement C3f and fibrinopeptide A (1466.929 ± 78.306 pg/ml, 4.189 ± 0.326 ng/ml, respevtively) in NAFLD group was higher than in control group (complement C3f 1159.357 ± 99.624 pg/ml, FPA 3.039 ± 0.483 ng/ml; P<0.05).

Conclusions: In this study, we established apeptidomics pattern that could help distinguish NAFLD patients from their twin controls. The differently-regulated peptides identified in our study may be potential diagnostic markers or therapeutic targets for NAFLD.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. MALDI-TOF MS spectra of one twin pair's peptide profile using C18 resin.
(A) MALDI-TOF MS spectrum of the twin in the disease group. (B) MALDI-TOF MS spectrum of the twin in the control group.
Figure 2
Figure 2. MALDI-TOF MS spectrum of the peptide profile using C4 resin.
Figure 3
Figure 3. Box-blot of the discriminatory peak signal-intensities.
(A), (B), (C), (D) refer to signal-intensities of peaks1, 2, 4 and 5, respectively.
Figure 4
Figure 4. MALDI-TOF MS spectra of the discriminatory peaks.
(A) MALDI-TOF MS spectrum of peak1 (861Da) in the disease group. (B) MALDI-TOF MS spectrum of peak1 (861Da) in the control group.
Figure 5
Figure 5. Clustering for variables of the 18 discriminatory peaks.
(N1) The 11 up-regulated peaks in the disease group. (N2) The 7 down-regulated peaks in the disease group.
Figure 6
Figure 6. Clustering for individuals of the 126 samples.
(A) The 63 disease samples. (B) The 63 control samples.
Figure 7
Figure 7. Three-dimensional plot of the principal components of samples and indexes,respectively.
(A) Disease group. (B) Control group. (C) The up-regulated peaks. (D) The down-regulated peaks.
Figure 8
Figure 8. Receiver operated curves of peaks 10, 12 and 14.
Figure 9
Figure 9. Concentrations of FPA and Complement C3f in NAFLD group and control group, respectively.
(A) Concentrations of FPA in NAFLD group and control group. (B) Concentrations of Complement C3f in NAFLD group and control group.

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