Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing

使用下一代测序技术鉴定一组用于心脏移植后患者急性细胞排斥诊断的心内膜活检 microRNA

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作者:Tereza Nováková, Táňa Macháčková, Jan Novák, Petr Hude, Július Godava, Víta Žampachová, Jan Oppelt, Filip Zlámal, Petr Němec, Helena Bedáňová, Ondřej Slabý, Julie Bienertová-Vašků, Lenka Špinarová, Jan Krejčí

Conclusion

We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.

Methods

Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software.

Results

The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample.

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