Targeting Prognosis: EV miR-122-5p in Kids’ Hodgkin Lymphoma

Extracellular Vesicle miR-122-5p as a Prognostic Biomarker in Pediatric Classical Hodgkin Lymphoma

Abstract

Currently, risk stratification for pediatric Hodgkin lymphoma is based on clinical factors such as stage, bulk, and systemic symptoms. Novel minimally invasive biomarkers could enhance both prognosis and treatment strategies. Therefore, the plasma extracellular vesicles’ microRNA profile was characterized by small RNA sequencing in 36 classical Hodgkin lymphoma cases and these findings were confirmed in an extended cohort of 86 patients by RT-qPCR. It was found that the levels of miR-122-5p at diagnosis were significantly higher (p-value: 0.0002) in patients who relapsed compared to patients in remission. The 5-year event-free survival of cases with high and low levels of miR-122-5p was 65 ± 7% and 93 ± 4%, respectively. MiR-122-5p levels were significantly associated with clinical events in both univariate (p-value: 0.0009) and multivariate (p-value: 0.0037) analysis (hazard ratio 5.8). Target prediction analysis suggests an involvement in the polarization of immune cells. The phenotypic characterization of peripheral blood mononuclear cells in 12 patients showed significantly increased levels of CD4+ T-cells in cases with high miR-122-5p levels as compared to low levels (p-value: 0.048). Moreover, CCL17 (TARC) and IL-6 plasma levels at diagnosis were significantly higher as compared to healthy donors (p-value: ≤0.0001). MiR-122-5p could complement current prognostic assays to identify patients at high risk of relapse.

Simplified version

Current risk stratification for pediatric Hodgkin lymphoma is based on clinical factors such as stage, bulk, and systemic symptoms. However, there is growing interest in finding less invasive tools to improve both prognosis and treatment strategies.

Therefore, we analyzed small molecules called microRNAs found in blood-circulating extracellular vesicles. We found that at diagnosis the microRNA miR-122-5p is significantly elevated in patients who later experienced a relapse.

In fact, children with high levels of miR-122-5p had a 5-year event-free survival rate of 65%, compared to 93% in those with lower levels. Interestingly, higher levels of miR-122-5p were also associated with changes in the blood circulating immune cells and increased levels of inflammatory markers like CCL17 (TARC) and IL-6.

These findings suggest that miR-122-5p could be a valuable addition to current risk prediction tools to help identify high-risk patients earlier.

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