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血清补体C3f和纤维蛋白肽A是非酒精性脂肪性肝病潜在的新型诊断生物标志物:青岛双胞胎研究

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

作者信息

Xin Yong-Ning, Geng Ning, Lin Zhong-Hua, Cui Ya-Zhou, Duan Hai-Ping, Zhang Mei, Xuan Shi-Ying

机构信息

Qingdao Municipal Hospital, Qingdao, Shandong Province, PR China.

School of Medicine, Qingdao University, Qingdao, Shandong Province, PR China.

出版信息

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

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.

摘要

目的

比较患非酒精性脂肪性肝病(NAFLD)和未患该病的双胞胎之间不同的血清肽组模式,以助于理解NAFLD的发病机制并确定潜在的诊断和治疗靶点。

方法

在中国青岛,将63例NAFLD患者的肽组模式与其双胞胎健康对照进行比较。使用C18反相柱捕获并浓缩800 Da至3500 Da之间的肽,随后进行基质辅助激光解吸电离飞行时间质谱分析。通过基质辅助激光解吸电离串联飞行时间质谱进一步鉴定与NAFLD相关的肽序列。进行了进一步的验证研究。使用市售酶联免疫吸附测定试剂盒检测另外100份血清样本,分别计算补体C3f和纤维蛋白肽A的浓度。使用SPSS 17.0分别比较这两种肽在NAFLD组和对照组中的差异。

结果

与健康对照相比,NAFLD组中有11个峰(861.1、877.07、904.5、1206.57、1350.64、1518.7、1690.9、1777.94、2931.29、3190.4、3261.4)上调,7个峰(942.44、1020.47、1060.06、1211.7、1263.63、1449.76、2768.3)下调。分别源自补体C3f和纤维蛋白肽A的两种肽在区分NAFLD患者与其正常对照方面具有最高的受试者工作特征曲线值。在验证组中,NAFLD组中补体C3f和纤维蛋白肽A的浓度(分别为1466.929±78.306 pg/ml、4.189±0.326 ng/ml)高于对照组(补体C3f为1159.357±99.624 pg/ml,纤维蛋白肽A为3.039±0.483 ng/ml;P<0.05)。

结论

在本研究中,我们建立了一种肽组模式,可有助于将NAFLD患者与其双胞胎对照区分开来。我们研究中鉴定出的差异调节肽可能是NAFLD的潜在诊断标志物或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5991/4176972/e867300f0e88/pone.0108132.g001.jpg

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