2 microRNAs together may be useful disease biomarkers: Study
Diagnostic accuracy improved with combined test results of miR-21, miR-29a
The levels of two microRNAs are found altered in the bloodstream of adults with systemic sclerosis (SSc) compared with healthy people, according to a new study that suggests using these molecules as biomarkers of the disease.
Elevated levels of one of them, called miR-21, is associated with scar formation, and low levels of the other, called miR-29a, is linked to suppression of scarring. These miRNAs may play a role in disease development and, when combined, may serve as diagnostic biomarkers, researchers suggest.
“Further analysis with higher number of patients is needed to confirm if these miRNAs could be used in the clinical practice as diagnostic biomarkers as well as biomarkers for both disease activity and progression,” they wrote in the study “Serum miR-21 and miR-29a expression in systemic sclerosis patients,” which was published in the journal Clinical and Experimental Rheumatology.
Biomarkers needed to improve early diagnosis, treatment of SSc
SSc is a chronic disorder marked by excessive scarring, or fibrosis, of the skin and potentially internal organs, and by blood vessel disease and abnormal immune responses. Because of the wide range of symptoms patients experience, specific biomarkers of SSc are needed to improve early diagnosis and to track disease progression and response to treatments.
MicroRNAs, or miRNAs, are emerging as potential biomarkers for several diseases, including SSc. These small RNA molecules regulate the activity of one or more genes in cells, thus controlling protein production.
miR-21 is found in most cell types and has been shown to play a role in the fibrotic process, as seen in SSc. By contrast, miR-29a is considered an anti-fibrotic miRNA, which targets and reduces the activity of fibrosis-related genes.
Scientists at the Medical University of Sofia, in Bulgaria, collected blood samples from 34 adults (31 women) with SSc to assess the utility of miR-21 and miR-29a as biomarkers. A group of 14 healthy individuals served as controls.
“The aim of our study was to evaluate the diagnostic value of serum miR21 and miR-29a expression [production] levels in SSc patients with regard to their use as diagnostic biomarkers in clinical practice,” the researchers wrote.
Tests of blood serum, the liquid portion of blood without cells or blood clotting proteins, showed miR-21 was elevated in half of the patients (50%). In comparison, levels of miR-29a were lower in 44.12% of the serum of SSc patients.
Based on these results, the ability of miR-21 to identify people with SSc, called sensitivity, was 64.7%. Likewise, the ability of miR-21 to rule out SSc, or its specificity, was 64.3%. Both findings were statistically non-significant, showing that “levels of miR-21 could not discriminate SSc patients from [healthy controls],” the team wrote.
Results with miR-29a were similar, with a sensitivity of 64.3% and specificity of 52.9%, also not reaching statistical significance.
Combining results of the 2 mRNAs significantly improved diagnostic accuracy
However, by combining the results of miR-21 and miR-29a, the diagnostic accuracy improved, with a sensitivity of 79.4% and specificity of 42.9%, a statistically significant difference.
Serum levels of miR-21 significantly correlated with levels of miR29a. They were also associated with either low or high levels of blood-clotting platelets, as well as hemoglobin, the protein in red blood cells that carries oxygen.
miR29a correlated with the presence of disease-related anti-Scl70 antibodies, which are related to SSc severity and lung involvement.
No associations were found between miR-21 and miR-29a and disease duration, organ involvement, capillaroscopic pattern (an assessment of blood vessel disease), and the use of disease-modifying antirheumatic drugs. There was a correlation between the capillaroscopic pattern and duration of illness, and lung fibrosis.
“Our data showed a deregulation of miR-21 and miR-29a in the serum of patients with SSc which could suggests their potential role in the disease pathogenesis [development],” the researchers wrote.
“Further analysis with higher number of patients is needed to confirm if these miRNAs could be used in the clinical practice as diagnostic biomarkers as well as biomarkers for both disease activity and progression,” the researchers added.