Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These cargo molecules are encapsulated in a lipid bilayer and internalized by target cells through receptor-ligand interactions or lipid membrane fusion. With the advancement of exosome research, exosome therapy for osteoporosis is fast becoming a research hotspot for researchers. This review aims to discuss the role of exosomes in the pathogenesis of osteoporosis. In addition, emerging diagnostic and therapeutic properties of exosomes are described to highlight the potential role of exosomes in osteoporosis.

Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. Homeobox (HOX) family genes are transcription factors that play a crucial role in anterior-posterior body axis patterning during embryonic development. This study aimed to propose a novel HOX-related signature of PGs to predict patients’ prognosis and immune infiltrate characteristics. Methods: Multiple levels of data (whole-exome sequencing, mRNA-sequencing, and single-cell RNA-sequencing) of 571 PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes, prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. A total of 39 HOX family genes were utilized to identify heterogeneous subtypes using consensus clustering. Then a random forest-supervised classification algorithm and a nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training group and validated in two test groups and an independent cohort. Results: Here, we first identified 39 HOX family genes significantly differentially expressed in PGs compared to adjacent normal tissues. Then the individuals with PGs were then divided into two heterogeneous clusters (cluster 1 and cluster 2) based on HOX family gene expression profiles. Cluster 2 showed higher total mutation counts, lower immune infiltration, and worse prognosis than cluster 1. Finally, we constructed a four-hub-HOX gene signature (including HOXA2, HOXA6, HOXC5, and HOXC6) based on the cluster for subtype prediction applying a random forest supervised classification algorithm and a nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis. Conclusion: Our results provide a novel method for the prognosis classification of PGs. The findings also suggest that the four-hub-HOX gene signature is a new biomarker for the prognosis of patients with PGs, allowing for more accurate survival prediction. Citation Format: Qianhao Zhao, Junyan Su. The HOX family gene signature predicts prognosis and indicates immune infiltrates in pediatric gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1396.