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The predictive value of selected serum microRNAs for acute GVHD by TaqMan MicroRNA arrays

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Abstract

Currently, the diagnosis of acute graft-versus-host disease (aGVHD) is mainly based on clinical symptoms and biopsy results. This study was designed to further explore new no noninvasive biomarkers for aGVHD prediction/diagnosis. We profiled miRNAs in serum pools from patients with aGVHD (grades II–IV) (n = 9) and non-aGVHD controls (n = 9) by real-time qPCR-based TaqMan MicroRNA arrays. Then, predictive models were established using related miRNAs (n = 38) and verified by a double-blind trial (n = 54). We found that miR-411 was significantly down regulated when aGVHD developed and recovered when aGVHD was controlled, which demonstrated that miR-411 has potential as an indicator for aGVHD monitoring. We developed and validated a predictive model and a diagnostic model for aGVHD. The predictive model included two miRNAs (miR-26b and miR-374a), which could predict an increased risk for aGVHD 1 or 2 weeks in advance, with an AUC, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of 0.722, 76.19 %, and 69.70 %, respectively. The diagnostic model included three miRNAs (miR-28-5p, miR-489, and miR-671-3p) with an AUC, PPV, and NPV of 0.841, 85.71 % and 83.33 %, respectively. Our results show that circulating miRNAs (miR-26b and miR-374a, miR-28-5p, miR-489 and miR-671-3p) may serve as biomarkers for the prediction and diagnosis of grades II–IV aGVHD.

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Acknowledgments

We would like to thank the staff in the Department of Clinical Biochemistry and Department of Hematology at the Chinese PLA General Hospital for their support and guidance. This research was supported by the National Natural Science Foundation of China (NO.81501821, NO.21375133), the China Postdoctoral Science Foundation (No.2015M572760, 2016T90989), and the National High Technology Research and Development Program of China (863 Program) (2011AA 02A 111). Written consent for publication was obtained from either the patients or their relatives.

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Authors and Affiliations

  1. Core Laboratory of Translational Medicine, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing, 100853, China

    Chunyan Zhang, Pengjun Zhang, Yuan Luo & Ya-Ping Tian

  2. Genetic and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe E Rd, Zhengzhou, 450052, China

    Nan Bai

  3. Department of Hematology, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing, 100853, China

    Wenrong Huang & Shuhong Wang

  4. Department of Clinical Biochemistry, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing, 100853, China

    Shasha Men, Ting Wen, Hongli Tong & Ya-Ping Tian

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  1. Chunyan Zhang
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Correspondence to Ya-Ping Tian.

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Chunyan Zhang, Yaping Tian, Wenrong Huang designed the study. Shasha Men and Ting Wen recruited the samples and clinical information. Nan Bai, Pengjun Zhang and Hongli Tong performed real-time PCR test. Chunyan Zhang, Yuan Luo and Wenrong Huang performed data analysis and interpretation; Chunyan Zhang and Yaping Tian wrote the manuscript. The corresponding author and all of the authors have read and approved the final submitted manuscript. None of the authors had a personal or financial conflict of interest.

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Zhang, C., Bai, N., Huang, W. et al. The predictive value of selected serum microRNAs for acute GVHD by TaqMan MicroRNA arrays. Ann Hematol 95, 1833–1843 (2016). https://doi.org/10.1007/s00277-016-2781-0

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