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Transplantation. 2019 Jan 30. doi: 10.1097/TP.0000000000002587. [Epub ahead of print]

Tolerance Biomarkers in Liver Transplantation: Independent External Validation of the Predictive Strength of SENP6 and FEM1C Gene Expression.

Author information

1
Biomedical Informatic and Bioinformatic Platform, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), University Clinical Hospital 'Virgen de la Arrixaca,' University of Murcia, Murcia, Spain.
2
Experimental Gastroenterology and Solid Organ Transplantation Lab, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), University Clinical Hospital 'Virgen de la Arrixaca,' University of Murcia, Murcia, Spain.
3
Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Instituto de Investigación Sanitaria de Navarra (IdiSNA).
4
General Surgery and Liver Transplantation Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
5
Division of Gastroenterology and Hepatology, University Hospital Virgen de la Arrixaca, Murcia, Spain.

Abstract

BACKGROUND:

Numerous studies have emphasized the genetic and phenotypic profiles of tolerant transplant patients. Moreover, different groups have defined several biomarkers, trying to distinguish patients who are going to be tolerant from those who are going to reject. However, most of these biomarkers have not been validated by other groups or even established for clinical practice.

METHODS:

We reanalyzed and stratified the predictive capacity of 20 previously described biomarkers for liver transplantation tolerance in a cohort of 17 liver transplant patients subjected to an independent, nonrandomized, prospective study of immunosuppression drug withdrawal.

RESULTS:

Only 4 of the 20 studied biomarkers (expression of SENP6, FEM1C, miR31 and miR95) showed a strong predictive capacity in the present study. miR31 and FEM1C presented an area under the ROC curve (AUC) of 96.7 %, followed by SENP1 with 93.3 %. Finally, miR95 had an AUC value below 86.7 %.

CONCLUSIONS:

Even though this independent analysis seems to confirm the predictive strength of SENP6 and FEM1Cin liver transplantation tolerance, there are also risks in establishing biomarkers for clinical phenotypes without an understanding of how they are biologically relevant. Future collaborations between groups should be promoted so that the most promising biomarkers can be validated and implemented in daily clinical practice.

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