Platelets (Apr 2022)

Potential biomarkers for inherited thrombocytopenia 2 identified by plasma proteomics

  • Xiaojie Wang,
  • Maoshan Chen,
  • Limeng Dai,
  • Chengning Tan,
  • Lanyue Hu,
  • Yichi Zhang,
  • Yanni Xiao,
  • Fengjie Li,
  • Cheng Zeng,
  • Zheng Xiang,
  • Yali Wang,
  • Weiwei Zhang,
  • Xiaomei Zhang,
  • Qian Ran,
  • Zhongjun Li,
  • Li Chen

DOI
https://doi.org/10.1080/09537104.2021.1937594
Journal volume & issue
Vol. 33, no. 3
pp. 443 – 450

Abstract

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Inherited thrombocytopenia 2 (THC2) is difficult to diagnose due to the lack of specific clinical characteristics and diagnostic methods. To identify potential plasma protein biomarkers for THC2, we collected the plasma samples from a THC2 family (9 THC2 and 15 non-THC2 members), enriched the medium and low abundant proteins using Proteominer and analyzed the protein profiles using the liquid chromatography-mass spectrometry in data independent acquisition mode. Initially, we detected 784 proteins in the plasma samples of this family and identified 27 up-regulated and 36 down-regulated in the THC2 group compared to the non-THC2 group (|log2 ratio| >1 and p-value <0.05). To improve the predictive power, top eight dysregulated proteins (B7Z2B4, LTF, HP, ERN1, IGHV1-8, A0A0X9V9C4, VH6DJ, and D3JV41) were selected by an area under the curve-based random forest process to construct a clinical model. Multivariate analysis with random forest and support vector machine showed that the prediction model provided high discrimination ability for THC2 diagnosis (AUC: 1.000 and 0.967, respectively). The potential plasma protein biomarkers will be tested in more THC2 patients and other thrombocytopenia patients to further validate their specificity and sensitivity.

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