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Endothelial and circulating C19MC microRNAs are biomarkers of infantile hemangioma
Graham M Strub1, Andrew L Kirsh2, Mark E Whipple1
1Department of Otolaryngology - Head and Neck Surgery, University of Washington, Seattle, Washington, USA.
Abstract:
Infantile hemangioma (IH) is the most common vascular tumor of infancy, and it uniquely regresses in response to oral propranolol. MicroRNAs (miRNAs) have emerged as key regulators of vascular development and are dysregulated in many disease processes, but the role of miRNAs in IH growth has not been investigated. We report expression of C19MC, a primate-specific megacluster of miRNAs expressed in placenta with rare expression in postnatal tissues, in glucose transporter 1-expressing (GLUT-1-expressing) IH endothelial cells and in the plasma of children with IH. Tissue or circulating C19MC miRNAs were not detectable in patients having 9 other types of vascular anomalies or unaffected children, identifying C19MC miRNAs as the first circulating biomarkers of IH. Levels of circulating C19MC miRNAs correlated with IH tumor size and propranolol treatment response, and IH tissue from children treated with propranolol or from children with partially involuted tumors contained lower levels of C19MC miRNAs than untreated, proliferative tumors, implicating C19MC miRNAs as potential drivers of IH pathogenesis. Detection of C19MC miRNAs in the circulation of infants with IH may provide a specific and noninvasive means of IH diagnosis and identification of candidates for propranolol therapy as well as a means to monitor treatment response.
Insights
New research identifies C19MC microRNAs (miRNAs) as the first circulating biomarkers for infantile hemangioma (IH). These miRNAs are detectable in IH tumors and infant blood, offering a potential diagnostic and monitoring tool for this common vascular tumor.
Area of Science:
- Vascular Biology
- Developmental Biology
- Genetics
Background:
- Infantile hemangioma (IH) is the most common vascular tumor in infants, uniquely responsive to propranolol treatment.
- MicroRNAs (miRNAs) regulate vascular development, but their role in IH pathogenesis is unexplored.
- C19MC miRNAs, typically placental, show rare postnatal expression.
Purpose of the Study:
- Investigate the role of C19MC miRNAs in infantile hemangioma (IH).
- Determine if C19MC miRNAs can serve as diagnostic biomarkers for IH.
- Assess the correlation between C19MC miRNA levels and IH tumor characteristics or treatment response.
Main Methods:
- Analyzed C19MC miRNA expression in IH tissue and plasma from infants.
- Compared C19MC miRNA levels in IH patients versus those with other vascular anomalies and healthy children.
- Correlated circulating C19MC miRNA levels with IH tumor size and propranolol treatment status.
Main Results:
- C19MC miRNAs were detected in GLUT-1-expressing IH endothelial cells and plasma, but not in other vascular anomalies or controls.
- Circulating C19MC miRNA levels correlated significantly with IH tumor size and response to propranolol.
- Lower C19MC miRNA levels were observed in treated or involuted IH compared to untreated, proliferative tumors.
Conclusions:
- C19MC miRNAs are the first specific circulating biomarkers for infantile hemangioma (IH).
- These miRNAs show potential for noninvasive IH diagnosis and monitoring of propranolol therapy effectiveness.
- C19MC miRNAs may play a role as drivers in IH pathogenesis.
