Identification of MYCN non-amplified neuroblastoma subgroups points towards molecular signatures for precision prognosis and therapy stratification.

BACKGROUND: Despite the extensive study of MYCN-amplified neuroblastomas, there is a significant unmet clinical need in MYCN non-amplified cases. In particular, the extent of heterogeneity within the MYCN non-amplified population is unknown. METHODS: A total of 1566 samples from 16 datasets were identified in Gene Expression Omnibus (GEO) and ArrayExpress. Characterisation of the subtypes was analysed by ConsensusClusterPlus. Independent predictors for subgrouping were constructed from the single sample predictor based on the multiclassPairs package. Findings were verified using immunohistochemistry and CIBERSORTx analysis. RESULTS: We demonstrate that MYCN non-amplified neuroblastomas are heterogeneous and can be classified into 3 subgroups based on their transcriptional signatures. Within these groups, subgroup_2 has the worst prognosis and this group shows a 'MYCN' signature that is potentially induced by the overexpression of Aurora Kinase A (AURKA); whilst subgroup_3 is characterised by an 'inflamed' gene signature. The clinical implications of this subtype classification are significant, as each subtype demonstrates a unique prognosis and vulnerability to investigational therapies. A total of 420 genes were identified as independent subgroup predictors with average balanced accuracy of 0.93 and 0.84 for train and test datasets, respectively. CONCLUSION: We propose that transcriptional subtyping may enhance precision prognosis and therapy stratification for patients with MYCN non-amplified neuroblastomas.

The efficacy of extracted Tanshinone compounds for infantile hemangiomas of the skin: results from a pilot study.

Background: Infantile hemangiomas (IHs) on skin are conventionally treated with beta blockers, pulsed dye laser (PDL), or surgery, either invasive or limited to clinical conditions. Our preclinical studies suggested that Tanshinone, extracted from Salvia miltiorrhiza (Tanshin), had a beneficial effect on IHs. Thus, we conducted a pilot clinical study to evaluate the safety and efficacy of topical Tanshinone compounds on superficial IHs. Methods: The single-armed pilot study included a total of 29 infants diagnosed with IHs. Thrice daily (at an interval of 6-8 hours) topical applications of Tanshinone were used for each patient. The primary response was the skin erythema index assessed by investigators using SkinColorCatch colorimeter instrument (Delfin). The Achauer score and the satisfaction of parents were also evaluated. Results: A total of 29 infants, 22 females (76%) and 7 males (24%), with a median age of 60 days (interquartile range, 45 to 99 days) were included. The position of IHs was distributed in the trunk (44.8%), head (34.5%), and limbs (20.7%). After 6 months of IHs treatment, the decrease in skin erythema index (baseline: 566.79±854.67 vs. after treatment: 467.97±1,118.39, P<0.001) was indicated. A total of 79.31% [23/29] of parents of the participants reported satisfaction on the responses after treatment. No serious side effects were documented. Conclusions: The topical use of Tanshinone compounds might be a potentially effective and noninvasive therapy in treating IHs.