Circulating miR-28-5p is a potential biomarker of sarcopenia in patients with Cushing’s syndrome in remission

E. Casademunt*^a (Dr), JS. Ibáñez-Cabello^b (Dr), M. Seco-Cerver^c (Dr), JL. García-Giménez^b (Dr), L. Martel-Duguech^d (Dr), S. Ruiz^a (Dr), J. Gil^a (Dr), M. Puig-Domingo^a (Prof), S. Webb^d (Prof), E. Valassi^a (Prof)

^a Hospital Universitari Germans Trias i Pujol, Badalona, SPAIN ; ^b Consortium Center for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona, SPAIN ; ^c Departamento de Fisiología, Facultat de Medicina i Odontología, Universidad de Valencia, Valencia, SPAIN ; ^d IIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau, Barcelona, SPAIN

* elenacg95@gmail.com

Background:

Patients with Cushing’s syndrome (CS) in remission present with sustained sarcopenia.

Changes in circulating levels of muscle-specific microRNAs (myomiRs) have been described in several conditions associated with muscle dysfunction, including aging-related sarcopenia. Our study was aimed at evaluating if there are differentially expressed myomiRs in plasma of patients with CS in remission, and these are related to sarcopenia.

Patients and methods:

Thirty-six women with CS in remission [median age (interquartile range), 51 (15); mean (±SD) BMI, 27±4 Kg/m2] and 36 age-, BMI-matched

female controls were included. Seven patients had sarcopenia according to the definition of the European Working Group on Sarcopenia in Older People (EWGSOP).

We performed small RNA sequencing to identify circulating miRNAs which are differentially expressed in CS patients as compared with controls. Small RNA libraries were generated and indexed using a modified Illumina TruSeq small RNA protocol. Significant miRNAs were identified using bioinformatic analysis, and validation was carried out using RT-Qpcr. For the validation, Taqman probes were performed on QuantStudio 5 equipment (Applied Biosystems).

Results:

MiR-28-5p, miR-495-3p and miR-654-5p were upregulated in CS patients as compared with controls (p<0.05). Expression of circulating miR-28-5p was significantly higher in CS patients with sarcopenia as compared with those without (AUC for fold-change, 0.798; p=0.0156). The optimised cut-off value for miR-28-5p to identify CS patients with sarcopenia was 3.80, which yielded a sensitivity of 85,71% and a specificity of 68,97%.

Conclusion:

MiR-28-5p, a myomiR involved in myotube proliferation and differentiation in vivo, may serve as an independent biomarker for identifying CS patients at high-risk of sarcopenia despite biochemical remission.

The author has declared no conflict of interest.