Biomarkers associated with progression of infantile hemangioma: Exploratory study

To identify patients with infantile hemangioma (IH) in need of early-stage treatment in this multicenter, prospective, observational study, we investigated the potential of plasma cytokines as a clinically useful marker. Plasma samples were collected at three time points from 41 patients with infantile hemangioma: baseline (days 14–60 after delivery), visit 1 (days 61–150, the proliferative phase), and visit 2 (days 151–395, the involuting phase). With a twofold or more increase in tumor volume during the baseline–visit 1 period regarded as progression, progression was seen in 15 cases (36.6%). In the first step, cytokine arrays were performed using plasma samples in five progressive and five non-progressive cases. Plasma levels of six cytokines at baseline were selected for a prediction marker of change in tumor volume during baseline–visit 1. Validation enzyme-linked immunosorbent assay indicated that the baseline growth differentiation factor 1 (GDF1) concentration tended to correlate with the proliferation ratio of total lesions or target lesion during baseline–visit 1, although without statistical significance. However, the plasma GDF1 concentrations were significantly lower in patients with a fourfold or more increase in total volume (p = 0.013). Furthermore, changes in plasma interleukin (IL)-7Rα levels showed a statistically significant inverse correlation between volume change of the target lesion during baseline–visit 1 (p = 0.0069). Our results suggest that plasma GDF1 measurement after birth is a useful marker for progression of IH. Additionally, the downregulation of IL-7Rα that begins several months after birth may also contribute to tumor growth. (UMIN-CTR: UMIN000038574).