Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma Proliferation

Abstract

Background Hemangiomas are unique endothelial cell tumors that spontaneously involute, which makes it difficult to interpret response to therapies. The objective of this work was to identify a potential biomarker in the urine of children with infantile hemangiomas that would facilitate testing new therapies. Methods A prospective longitudinal study in children with hemangiomas and age matched healthy controls was performed to determine whether microRNA (miR)-126, which is highly abundant in fetal endothelial cells, was more abundant in the urine of affected children. Prospective ultrasound measurements of hemangioma size and blood flow velocity were obtained as secondary endpoints to document longitudinal changes in untreated hemangiomas. Results Urinary miR-126 levels were significantly elevated in children with proliferating hemangiomas and relative levels of urinary miR abundance correlated with hemangioma size. Hemangiomas had elevated levels of miR abundance compared to healthy controls. Ultrasound data revealed that hemangioma proliferation typically stopped between 6 to 9 months of age. When hemangioma proliferation stopped urinary miR-126 levels in children with hemangiomas dropped to levels observed in healthy age matched controls. Conclusions These are the first reported results to identify a potential miR biomarker in the urine of children with hemangiomas. Measurement of urinary levels of miR-126 could potentially be used to monitor hemangioma response to therapies.

Identification of putative biomarkers for Infantile Hemangiomas and Propranolol treatment via data integration

“…From Strub et al 23 , we selected members of the C19MC microRNAs found in blood that showed changes between pre-treatment and 1 or 6 months of propranolol exposure. Biswas et al 28 reported that microRNA 126 as a biomarker for the proliferative phase of infantile hemangiomas; however, it was not clear from their report which mature form (miR-126-3p or miR-126-5p) was used for their comparisons. In both of the previous studies, microRNA quantification was performed with RT-PCR that precluded us from re-analyzing raw data for better data integration.…”

Morphological, genetic and clinical correlations in infantile hemangiomas and their mimics

“…Biswas et al identified increased urinary levels of miRNA-126 in children with a proliferative hemangioma and managed to establish a proliferation window between six and nine months of age. Afterwards, the levels of miRNA-126 in urine dropped to values encountered in healthy age-matched controls [23].…”

“…RBFOX2 gene is a member of the Rbfox-splicing factors, and it is responsible for the alternative splicing in vascular CaV1.2 channels, which have a regulatory role for intramural pressure change because of blood flow fluctuations [21]. It has been suggested that RBFOX2 could be used as a biomarker, along with Doppler ultrasound in order to establish IH development sites based on expression levels and flow velocities [18,22,23].…”

“…Tissue miRNA profiling may be a tool for the differential diagnosis between IHs and non-involuting congenital hemangioma, a tumor that does not respond to Propranolol treatment [24]. Even more, the chromosome 19 miRNA cluster proved to be an effective therapy control biomarker, since its levels decreased in Propranolol-treated and involuted cases, while other miRNAs levels were unaffected [23,25].…”

Reply: Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma Proliferation

“…Thank you for your thoughtful comments about our recent article, “Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma Proliferation.” 1 The National Institutes of Health Biomarkers Definition Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” 2 There is no requirement that a biomarker represent a singular biologic molecule only found in hemangiomas. The temporal changes in urinary microRNA-126 (miR-126) abundance provided the evidence that miR-126 expression correlates with hemangioma growth with significantly elevated levels during proliferation and no differences with unaffected healthy controls at 9 months of age, when hemangioma proliferation has generally ended.…”