Identification of a detection panel for post-transplant virus infection through integrated analysis of non-coding RNAs in peripheral blood

Abstract Viral infection seriously affects the survival and life quality of transplanted patients without an accurate diagnosis during the early stage. Herein, we aimed to develop a novel diagnostic method based on non-coding RNAs expression in peripheral blood. An immunosuppressive mouse model of viral infection after transplantation was established. Differentially expressed non-coding RNAs were distinguished by microarray analyses in the virus-infected group. After homology analysis, 46 miRNAs and 24 lncRNAs were further verified by qRT-PCR in the peripheral blood samples of transplanted patients. Compared with normal transplanted patients, miR-29b, miR-185, and NR_073415.2 were significantly downregulated in the PBMC of post-transplant patients with viral infection. Based on the expression of the above three RNAs, principal component analysis (PCA) identified a slight overlap between the two groups. A 3-non-coding-RNA detection panel was constructed by the support vector machine analysis (SVM), whose loss rate was 14.71%. The area under the curve of it was 0.909. With the optimal cut-off value (Y = 0.328), the sensitivity was 0.929 and the specificity was 0.781. Therefore, based on non-coding RNAs expressions, a detection panel for viral infection after organ transplantation was formed with high diagnostic specificity and sensitivity.

[1]  M. Moghoofei,et al.  The role of HPV gene expression and selected cellular MiRNAs in lung cancer development. , 2020, Microbial pathogenesis.

[2]  T. Asselah,et al.  miRNAs as Potential Biomarkers for Viral Hepatitis B and C , 2020, Viruses.

[3]  N. Rouphael,et al.  The Role of Systems Vaccinology in Understanding the Immune Defects to Vaccination in Solid Organ Transplant Recipients , 2020, Frontiers in Immunology.

[4]  R. Xu,et al.  LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer , 2020, Cancer communications.

[5]  A. Limaye,et al.  Progress and Challenges in the Prevention, Diagnosis, and Management of Cytomegalovirus Infection in Transplantation , 2020, Clinical Microbiology Reviews.

[6]  G. Goodall,et al.  RNA in cancer , 2020, Nature reviews. Cancer.

[7]  Di Wu,et al.  An Autophagy-Related Gene Signature Associated With Clinical Prognosis and Immune Microenvironment in Gliomas , 2020, Frontiers in Oncology.

[8]  W. Hwang,et al.  Gene signature of antigen processing and presentation machinery predicts response to checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma , 2020, Journal for ImmunoTherapy of Cancer.

[9]  Arash Salmaninejad,et al.  Exosomal microRNAs: novel players in cervical cancer. , 2020, Epigenomics.

[10]  S. Mostafaei,et al.  MicroRNAs Profiling in HIV, HCV and HIV/HCV Coinfected Patients. , 2020, Current HIV research.

[11]  Kang Lin,et al.  A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis , 2020, Journal of cellular physiology.

[12]  G. Brandi,et al.  Is post‐transplant chemotherapy feasible in liver transplantation for colorectal cancer liver metastases? , 2020, Cancer communications.

[13]  Michael R Hamblin,et al.  Circular RNAs: New Epigenetic Signatures in Viral Infections , 2020, Frontiers in Microbiology.

[14]  Dongjie Chen,et al.  Identification of a 4-lncRNA signature predicting prognosis of patients with non-small cell lung cancer: a multicenter study in China , 2020, Journal of Translational Medicine.

[15]  M. Moghoofei,et al.  The assessment of selected MiRNAs profile in HIV, HBV, HCV, HIV/HCV, HIV/HBV Co-infection and elite controllers for determination of biomarker. , 2020, Microbial pathogenesis.

[16]  Guodong Yang,et al.  A Five-microRNA Signature as Prognostic Biomarker in Colorectal Cancer by Bioinformatics Analysis , 2019, Front. Oncol..

[17]  Xunrong Luo,et al.  Impact of infection on transplantation tolerance , 2019, Immunological reviews.

[18]  F. Slack,et al.  The Role of Non-coding RNAs in Oncology , 2019, Cell.

[19]  M. Haleyurgirisetty,et al.  Development and validation of plasma miRNA biomarker signature panel for the detection of early HIV-1 infection , 2019, EBioMedicine.

[20]  Peitang Huang,et al.  miR-21-3p Regulates Influenza A Virus Replication by Targeting Histone Deacetylase-8 , 2018, Front. Cell. Infect. Microbiol..

[21]  G. Javorsky,et al.  Parvovirus B19 Induced Red Cell Aplasia in a Heart Transplant Patient Diagnosed on Pleural Fluid. , 2018, Transplantation.

[22]  Nina Singh,et al.  Viral infections in solid organ transplant recipients: novel updates and a review of the classics , 2017, Current opinion in infectious diseases.

[23]  T. Cech,et al.  How do lncRNAs regulate transcription? , 2017, Science Advances.

[24]  J. Fishman.  Infection in Organ Transplantation , 2017, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[25]  S. Vienberg,et al.  MicroRNAs in metabolism , 2016, Acta physiologica.

[26]  R. Chung,et al.  Long noncoding RNAs expressed in human hepatic stellate cells form networks with extracellular matrix proteins , 2016, Genome Medicine.

[27]  Chun Yang,et al.  Oil species identification technique developed by Gabor wavelet analysis and support vector machine based on concentration-synchronous-matrix-fluorescence spectroscopy. , 2016, Marine pollution bulletin.

[28]  Rodney K. Lyn,et al.  MicroRNAs regulate the immunometabolic response to viral infection in the liver. , 2015, Nature chemical biology.

[29]  A. Shalev,et al.  β-Cell MicroRNAs: Small but Powerful , 2015, Diabetes.

[30]  S. Yamanaka,et al.  A developmental framework for induced pluripotency , 2015, Development.

[31]  D. Sawinski,et al.  BK virus infection: an update on diagnosis and treatment. , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[32]  F. Marcucci,et al.  microRNA levels in paraffin-embedded indolent B-cell non-Hodgkin lymphoma tissues from patients chronically infected with hepatitis B or C virus , 2014, BMC Infectious Diseases.

[33]  S. Wen,et al.  EphB2 contributes to human naive B‐cell activation and is regulated by miR‐185 , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  A. Fatica,et al.  Long non-coding RNAs: new players in cell differentiation and development , 2013, Nature Reviews Genetics.

[35]  Jennifer L. Eitson,et al.  Transgenic Expression of MicroRNA-185 Causes a Developmental Arrest of T Cells by Targeting Multiple Genes Including Mzb1* , 2013, The Journal of Biological Chemistry.

[36]  J. Markmann,et al.  Historical overview of transplantation. , 2013, Cold Spring Harbor perspectives in medicine.

[37]  J. Mendell,et al.  MicroRNAs in Stress Signaling and Human Disease , 2012, Cell.

[38]  D. Diamond,et al.  The immune response to human CMV. , 2012, Future virology.

[39]  D. Brennan,et al.  Epstein-Barr virus and renal transplantation. , 2017, Transplantation reviews.