A Systems Analysis of the Relationships Between Anemia and Ischemic Stroke Rehabilitation Based on RNA-Seq Data.

Yingying Wang, Xingxian Huang, Jianfeng Liu, Xuefei Zhao, Haibo Yu, Yunpeng Cai
Author Information
  1. Yingying Wang: Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, China.
  2. Xingxian Huang: Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
  3. Jianfeng Liu: Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
  4. Xuefei Zhao: Institute of Harbin Hematology & Oncology, The First Hospital of Harbin, Harbin, China.
  5. Haibo Yu: Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
  6. Yunpeng Cai: Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, China.

Abstract

Ischemic stroke (IS) is one of the main causes of morbidity and disability worldwide due to its complex mechanism. Anemia was characterized as a risk factor of IS because the direct connection between central nervous system, blood supply, and tissue oxygen delivery. As the key oxygen-carrying molecule in the blood, hemoglobin (Hb) may be decisive in the destiny of penumbral area or influence the brain recovery and neurologic function, which could finally affect the outcome of IS. However, more detailed information on the expression levels of Hb related genes were still lacking possibly because the concentration of Hb was determined by the genes' expression several hours ago, which may make the research more difficult to perform. This time gap between gene expressions and protein concentration could make these genes predictive bio-markers for IS outcome. In this study, we choose 28 IS patients, of which 12 were suffering from anemia. Statistical analysis results showed that the outcomes of the patients were different when dividing them into two groups characterized by Hb concentration. 2 sex and age matched patients were first chosen to perform RNA-seq analysis on, on two occasions at two different time points, after which the Hb counts were tested at least 24 h after sequencing. Results showed that the outcome of anemia patients was poor compared with non-anemia patients. Two other patients were then chosen for analysis which excluded the coincidence of other factors. The results showed that the low value of Hb under 13 g/dL in men were closely related to the poor outcome of IS patients. Differently expressed Hb related genes were tested and six genes were shown to be positively correlated with the recovery degree of IS patients: ELANE, FGF23, HBB, PIEZO1, RASA4, and PRTN3. Gene CPM was shown to be negatively correlated with clinical outcomes. All of the seven genes were validated to be related to strokes using real-time PCR or literature searches. Taken together, these genes could be considered as new predictors for the recovery of IS patients.

Keywords

References

  1. Stroke. 2002 Oct;33(10):2363-6 [PMID: 12364722]
  2. J Clin Neurosci. 2009 May;16(5):645-9 [PMID: 19285409]
  3. Neurocrit Care. 2009 Dec;11(3):417-26 [PMID: 19548120]
  4. Crit Rev Clin Lab Sci. 2010 Mar-Apr;47(2):72-123 [PMID: 20590502]
  5. Cent Nerv Syst Agents Med Chem. 2011 Jun 1;11(2):114-37 [PMID: 21521171]
  6. Stroke. 2011 Oct;42(10):2832-7 [PMID: 21852622]
  7. Can J Neurol Sci. 2012 Mar;39(2):189-95 [PMID: 22343152]
  8. Neurology. 2013 Feb 19;80(8):719-24 [PMID: 23365064]
  9. Mol Imaging Biol. 2013 Aug;15(4):411-22 [PMID: 23400400]
  10. Stroke. 2013 Nov;44(11):3220-2 [PMID: 24003047]
  11. Mol Neurobiol. 2014 Feb;49(1):563-73 [PMID: 24026771]
  12. Neurology. 2014 May 13;82(19):1700-6 [PMID: 24706015]
  13. Acta Neurol Scand. 2015 Feb;131(2):132-9 [PMID: 25214428]
  14. Int J Stroke. 2015 Feb;10(2):224-30 [PMID: 25427291]
  15. J Ayub Med Coll Abbottabad. 2014 Apr-Jun;26(2):111-4 [PMID: 25603656]
  16. Int J Cardiol. 2015;186:117-24 [PMID: 25814357]
  17. J Renin Angiotensin Aldosterone Syst. 2015 Sep;16(3):681-6 [PMID: 25944852]
  18. BMC Med Genet. 2015 Jul 23;16:52 [PMID: 26201603]
  19. Cell Rep. 2015 Nov 10;13(6):1161-1171 [PMID: 26526998]
  20. Curr Opin Pharmacol. 2016 Apr;27:31-7 [PMID: 26874237]
  21. Genomics Proteomics Bioinformatics. 2017 Feb;15(1):14-18 [PMID: 28387199]
  22. Mol Immunol. 2017 Sep;89:69-72 [PMID: 28622911]
  23. Nucleic Acids Res. 2018 Jan 4;46(D1):D14-D20 [PMID: 29036542]
  24. BMC Genomics. 2018 Dec 31;19(Suppl 10):911 [PMID: 30598109]
  25. Front Genet. 2018 Dec 10;9:618 [PMID: 30619454]
  26. Front Genet. 2019 Feb 05;10:20 [PMID: 30804977]