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Experimental and molecular pathology v.103 no.2, 2017년, pp.163 - 171   SCIE SCOPUS
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

5-gene differential expression predicts stability of human intestinal allografts

Talayero, Paloma (Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain ) ; Alonso-Guirado, Lola (Bioinformatics and Biostatistics Unit, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain ) ; Padilla, Guillermo (Bioinformatics and Biostatistics Unit, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain ) ; Artaza, Haydee (Bioinformatics and Biostatistics Unit, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain ) ; Dopazo, Ana (Genomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain ) ; Sánchez-Cabo, Fátima (Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain ) ; Rodríguez-Muñoz, Sarbelio (Department of Gastroenterology, University Hospital 12 de Octubre, Madrid, Spain ) ; Calvo-Pulido, Jorge (Department of General and Digestive Surgery and Abdominal Organ Transplantation, University Hospital 12 de Octubre, Madrid, Spain ) ; Mancebo, Esther (Department of Immunology, University Hospital 12 de Octubre, Madrid, Spain ) ; de Lacoba, Mario García (Bioinformatics and Biostatistics Unit, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain ; ) ; Paz-Artal, Estela ;
  • 초록  

    Abstract In intestinal allografts, endoscopy and histology detect the injury once changes in the bowel wall architecture have occurred. We aimed to identify a molecular signature that could predict early deterioration, within histologically indistinguishable biopsies with “minimal changes” (MC) pathology. Sixty biopsies from 12 adult recipients were longitudinally taken during 8years post-transplant. They were classified as either stable (STA) or non-stable (NSTA) according to the prospectively recorded number, frequency and severity of rejection events of the allograft. In a discovery set of MC samples analyzed by RNA-Seq, 816 genes were differentially expressed in STA vs NSTA biopsies. A group of 5 genes (ADH1C, SLC39A4, CYP4F2, OPTN and PDZK1) correctly classified all NSTA biopsies in the discovery set and all STA biopsies from an independent set. These results were validated by qPCR in a new group of MC biopsies. Based on a logistic regression model, a cutoff of 0.28 predicted the probability of being a NSTA biopsy with 85% sensitivity and 69% specificity. In conclusion, by analyzing MC samples early after transplantation, the expression of a 5-gene set may predict the evolution of the bowel allograft. This prognostic biomarker may be of help to personalize care of the intestinal transplant recipient. Highlights RNA-Sequencing is a highly sensitive tool for biomarker discovery. Apparently histologically equal biopsies are molecularly different. A 5-gene signature may be able to predict intestinal graft stability.


  • 주제어

    Intestinal transplantation .   Graft stability .   Gene expression .   RNA-sequencing .   Biomarkers.  

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