Journal of Neurology

, Volume 265, Issue 11, pp 2573–2586 | Cite as

Peripheral tumor necrosis factor-a-induced protein 8-like 2 mRNA level for predicting 3-month mortality of patients with acute ischemic stroke

  • Yuan-Yuan Zhang
  • Na-Na Huang
  • Yu-Chen Fan
  • Yan-Shuang Li
  • Jing Zhao
  • Dong Wang
  • Feng Zhang
  • Xiao-Hong LiEmail author
Original Communication


Tumor necrosis factor-a-induced protein 8-like 2 (TIPE2) is a novel negative regulator for maintaining immune homeostasis. This study aimed to investigate TIPE2 mRNA in peripheral blood mononuclear cells for predicting 3-month functional outcomes and mortality of patients with acute ischemic stroke. A total of 182 consecutive patients were prospective collected, and there were 55 (30.2%) patients with unfavorable outcome and 33 (18.1%) patients died at the end of 3 months. The area under the operating characteristic curve (AUC) for TIPE2 mRNA was 0.810 (95% CI 0.733–0.886) for mortality and 0.740 (95% CI 0.662–0.818) for unfavorable outcome. The model incorporating National Institutes of Health Stroke Scale (NIHSS) plus TIPE2 showed significantly (P = 0.04) increased discrimination power (AUC = 0.925, 95% CI 0.874–0.976) for mortality than NIHSS (AUC = 0.882, 95% CI 0.833–0.932). Furthermore, NIHSS plus TIPE2 showed a significant improvement of both integrated discrimination index (IDI) and net reclassification index (NRI) as compared with NIHSS (IDI = 0.224, 95% CI 0.150–0.299, P < 0.001; NRI = 1.119, 95% CI 0.810–1.429, P < 0.001). The pruned time-dependent tree analysis showed that patients with NIHSS ≥ 5.5 and TIPE2 mRNA < 5.2 had rather high 3-month mortality. In conclusion, TIPE2 mRNA improved the diagnostic value of NIHSS score, and patients with NIHSS ≥ 5.5 and TIPE2 mRNA < 5.2 had high 3-month mortality.


Tumor necrosis factor-a-induced protein 8-like 2 Acute ischemic stroke Mortality Functional outcome Biomarker 



We greatly appreciated the technical assistance with statistical analysis during the revision provided by Prof. Tao Zhang (Department of Biostatistics, School of Public Health, Shandong University), and Dr. Xinglin Chen (EmpowerStat software, developed by the statistician Prof. Chang-Zhong Chen, Harvard University).


This work was supported by the Grant from the National Natural Science Foundation of China (81373635) and the Key Research and Development Plan of Shandong Province (2016GSF121044).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no competing interests.

Ethical statement

The study was approved by the local ethics committee of the Jinan Central Hospital affiliated to Shandong University.

Supplementary material

415_2018_9036_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 17 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyJinan Central Hospital affiliated to Shandong UniversityJinanChina
  2. 2.Department of HepatologyQilu Hospital of Shandong UniversityJinanChina

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