DOI: 10.1097/tp.0000000000004622 ISSN:

Combining Serum miR-144-3p and miR-652-3p as Potential Biomarkers for the Early Diagnosis and Stratification of Acute Cellular Rejection in Heart Transplantation Patients

Lorena Pérez-Carrillo, Ignacio Sánchez-Lázaro, Juan Carlos Triviño, Sandra Feijóo-Bandín, Francisca Lago, José Ramón González-Juanatey, Luis Martínez-Dolz, Manuel Portolés, Estefanía Tarazón, Esther Roselló-Lletí
  • Transplantation
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Background.

There is a dire need for specific, noninvasive biomarkers that can accurately detect cardiac acute cellular rejection (ACR) early. Previously, we described miR-144-3p as an excellent candidate for detecting grade ≥2R ACR. Now, we investigated the combination of miR-144-3p with miR-652-3p, other differentially expressed serum miRNA we previously described, to improve diagnostic accuracy mainly in mild rejection to avoid reaching severe stages.

Methods.

We selected miR-652-3p from a preliminary RNA-seq study to be validated by reverse transcription-quantitative polymerase chain reaction on 212 consecutive serum samples from transplantation recipients undergoing routine endomyocardial biopsies to subsequently combine them with miR-144-3p results and investigate their diagnostic capability.

Results.

We confirmed the miR-652-3p overexpression (P < 0.0001) and its capability to discriminate between patients with and without ACR of any grade (P < 0.0001). The combined serum levels of miR-144-3p and miR-652-3p were significantly higher in patients with rejection regardless of posttransplantation time (P < 0.0001). This combination resulted in a diagnostic efficacy for 1R (area under the curve = 0.794) and ≥2R (area under the curve = 0.892; P < 0.0001) that was superior to each biomarker alone. Furthermore, it was a strong independent predictor of ACR for 1R (odds ratio of 10.950; P < 0.0001) and ≥2R (odds ratio of 14.289; P < 0.01).

Conclusions.

We demonstrated that an appropriate combination of blood-based biomarkers could exhibit greater efficiency for cardiac rejection diagnosis. The combined detection of abnormal expression of miR-144-3p and miR-652-3p in the serum of ACR patients can improve the diagnostic sensitivity of rejection at an early stage and contribute to increasing the diagnostic accuracy, mainly in the lower rejection grades.

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