👤 Sonika Dahiya

High-grade astrocytoma with piloid features (HGAP) is a recently defined central nervous system (CNS) tumor, first introduced into the 2021 World Health Organization (WHO) classification. While predominantly observed in adults, pediatric cases remain rare and poorly characterized. This study aimed to review the epidemiology, clinical features, and molecular profile of pediatric HGAP. A comprehensive review of studies published from 2018 to 2025 was performed to identify methylation-confirmed HGAP cases in patients aged 18 years or younger. Data extracted from studies included subject demographics, tumor location, histological features, molecular alterations, and the implemented treatment sequence. The search identified 17 pediatric cases meeting the inclusion criteria. The median age at diagnosis was 15 years (range: 4-18 years), and a male predilection of approximately twofold was observed. Tumors most commonly arose in the posterior fossa (56.3%). Recurrent molecular alterations included CDKN2A/B loss (75%), FGFR1 mutations or fusions (55.6%), and ATRX loss (45.5%). This review did not identify definitive clinical or histomolecular differences between pediatric and adult HGAP, underscoring the need for further comparative studies. Pediatric HGAP may represent an underrecognized diagnostic entity within the glioma spectrum, emphasizing the critical role of methylation profiling for accurate diagnosis and classification. Retrospective reclassification of histologically and molecularly ambiguous gliomas is warranted and may reveal additional cases. Larger pediatric cohorts are urgently needed to inform clinical management and refine prognostic stratification. Show less

Though cholesterol accumulation is an established hallmark of a tumor cell, the relationship between the two is still not clear. Previously, we identified 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), Sterol Regulatory Element BindingTranscription Factor 2 (SREBF2), Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3), and Nuclear Receptor Subfamily 1 Group H Member 2 (NR1H2) as the key cholesterol homeostasis genes involved in colorectal cancer (CRC). In the present study, we aimed to identify microRNAs regulating these key genes in CRC. miR-18a-5p, miR-144-3p, and miR-663b were selected as the miRNAs targeting NR1H2, HMGCR, and SREBF2, respectively, based on the bioinformatic prediction tools and literature review. Their expression was evaluated in the local and The Cancer Genome Atlas (TCGA) cohorts. Receiver Operating Characteristic Curves and Kaplan Meier analysis were performed to elucidate their diagnostic and prognostic potential. Pearson or Spearman's correlations were used to evaluate the relationship between miRNAs and their target genes. Protein-protein interaction networks and Gene Ontology analyses were performed to investigate the potential molecular mechanism of these miRNAs. Deregulated expression of miR-18a-5p, miR-144-3p, and miR-663b was associated with various clinicopathological features. miR-18a-5p exhibited an inverse correlation with NR1H2. miR-18a-5p and miR-144-3p also had a significant direct correlation with miR-33a-5p, an important modulator of cholesterol homeostasis. These miRNAs also exhibited high centrality in the mirna-protein interaction network. miR-144-3p and miR-663b exhibited the potential to be used as diagnostic biomarkers. miR-18a-5p and miR-144-3p exhibited the potential to modulate cholesterol homeostasis in CRC. miR-663b is an interesting candidate in CRC pathophysiology. Show less

Accumulation of cholesterol is a well-known feature in cancer. Preclinical studies suggest the contribution of various cholesterol regulators in CRC. However, their clinical relevance remains poorly understood. The aim of the present study is to evaluate the expression of these modulators in CRC and elucidate their diagnostic and prognostic value. mRNA levels of HMGCR, SREBF2, NR1H3 and NR1H2 were downregulated in tumors in local and TCGA cohort. The expression of LDLR, ABCA1 and SCARB1 was not consistent in the two cohorts. Western Blot analysis showed the increased levels of LDLR and reduced levels of LXR in early stage patients. Tumoral SREBP2 levels were enhanced in early stage whereas decreased in late stage. The individual expression of HMGCR, SREBF2, NR1H3 and NR1H2 did not have the potential to be used as independent prognostic marker, however, the combined expression of these genes associated with poor clinical outcome independent of lymph node metastasis, distant metastasis and advanced stage. This work sheds light on deregulation of cholesterol uptake and efflux pathways and provides novel leads in the development of biomarkers and therapeutic regimens that can detect and target CRC at initial stages. Show less