MicroRNA levels may help predict CTEPH diagnosis: Study

miR-let7a may be biomarker to ID blood flow impairment, predict risk

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by Andrea Lobo |

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Blood levels of microRNA — small RNA molecules that regulate protein production — are decreased in people with pulmonary embolism (PE) compared with healthy people. PE is the cause of chronic thromboembolic pulmonary hypertension (CTEPH).

However, higher blood levels of miR-let7a were found in people with acute PE who were diagnosed with CTEPH during follow-up, according to a recent study.

“Therefore, miR-let7a might serve as a novel biomarker to identify patients with hemodynamic [blood flow] impairment and as a novel predictor for patients at risk for CTEPH,” the researchers wrote in “Circulating miR-let7a levels predict future diagnosis of chronic thromboembolic pulmonary hypertension,” which was published in Scientific Reports.

CTEPH is a rare form of pulmonary hypertension, a condition associated with high blood pressure in the blood vessels of the lungs, which develops from PE, a blockage in a pulmonary artery. Such blockages are caused by blood clots that travel from deep veins in the legs or other parts of the body.

Levels of microRNAs (miRNAs) vary depending on disease status and the specific type of cell. In recent years, miRNAs have emerged as new biomarkers for diagnosis and prognosis. However, “little is known about the miRNA profiles in patients with acute PR and CTEPH,” wrote researchers in Germany who investigated patterns of miRNA levels during acute PE and tested their value at predicting the risk of developing CTEPH. They used blood samples from 20 people with acute PE and 20 sex- and age-matched healthy people. The researchers then analyzed a commercially available panel of 754 human miRNAs.

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Evaluating levels of miRNAs

The levels of 53 miRNAs were significantly different in people with PE compared with samples from healthy participants. Three miRNAs — miR-29a, miR-720, and miR-let7a — were selected among the top 10 dysregulated miRNAs for validation. In PE patients, miR-29a and miR-720 were present at higher levels, or upregulated, while miR-let7a was downregulated.

In an independent group of patients, wherein 117 had a recurrent blood clotting event (53) or died (64), levels of miRNA-29a were higher when the number of new cases of recurrent events or death were also higher. The inverse association — lower levels and more events — was seen with miR-let7a.

Also, blood levels of miR-let7a significantly correlated with blood flow parameters associated with right heart dysfunction. In pulmonary hypertension, increased blood pressure in the lungs means the right side of the heart must work harder to pump blood, which can lead to heart failure.

The results underscored the clinical interest in miR-let7a, the researchers said.

A total of 3.4% of the participants with acute PE were diagnosed with CTEPH at follow-up. Among them, miR-let7a was significantly upregulated at the time of PE diagnosis compared to PE patients who didn’t develop CTEPH.

To see if circulating miR-let7a levels might tell how likely CTEPH is to occur in people with PE, the researchers calculated a measure called area under the curve. This is a test of how well a measure can differentiate between two groups. Values can range from 0.5 to 1, with higher values indicating a better ability to tell the two groups apart.

Findings showed miR-let7a levels could predict the patients who would be diagnosed with CTEPH with an AUC value of 0.767. Also, a miR-let7a cutoff value of or above 11.92 was associated with a 12.8-times increased risk of CTEPH. In this association, the sensitivity was 78% and the specificity was 31%. Sensitivity refers to a test’s ability to correctly identify people with a certain condition. Specificity is the ability to identify those without the condition.

Adjusting for age and sex didn’t affect the link between miR-let7a and CTEPH risk significantly.

“Further research is needed to determine whether miR-let7a may help in clinical decision-making and prognostic assessment of individual patients,” wrote the scientists, who said more research is needed to “evaluate if these miRNAs are specifically regulated in the acute phase of PE or also in the progression of the chronic disease.”

A Conversation With Rare Disease Advocates