Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Abstract

Osteosarcoma is the most common type of primary malignant bone tumor observed in children and adolescents. The aim of the present study was to identify an osteosarcoma-related gene module (OSM) by looking for a dense module following the integration of signals from genome-wide association studies (GWAS) into the human protein-protein interaction (PPI) network. A dataset of somatic mutations in osteosarcoma was obtained from the dbGaP database and their testing P-values were incorporated into the PPI network from a recent study using the dmGWAS bioconductor package. An OSM containing 201 genes (OS genes) and 268 interactions, which were closely associated with immune response, intracellular signal transduction and cell activity was identified. Topological analysis of the OSM identified 11 genes, including APP, APPBP2, ATXN1, HSP90B1, IKZF1, KRTAP10-1, PAK1, PDPK1, SMAD4, SUZ12 and TP53 as potential diagnostic biomarkers for osteosarcoma. The overall survival analysis of osteosarcoma for those 11 genes based on a dataset from the Cancer Genome Atlas, identified APP, HSP90B1, SUZ12 and IKZF1 as osteosarcoma survival-related genes. The results of the present study should be helpful in understanding the diagnosis and treatment of osteosarcoma and its underlying mechanisms. In addition, the methodology used in the present study may be suitable for the analysis of other types of disease.

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

“…Overexpression of IKZF1 can activate autoimmune susceptibility through infiltrating NKG2D+ and CD8+ T cells ( Chen et al, 2018a ). Its prognostic value has been noted in osteosarcoma ( Zhang and Yang, 2018 ). JCHAIN encodes the immunoglobulin J chain and links monomer units of IgA and IgM, and the upregulation of JCHAIN was likely related to tumor aggression, as studied in a cohort of patients with acute lymphoblastic leukemia (ALL) who had died ( Tomar et al, 2019 ).…”

MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to activate the AKT/mTOR signaling pathway

“…Unlike the exploration of downstream targets in the previous study [29] , we dug into the regulation mechanism of miR-451a on the oncogenic AKT/mTOR signaling pathway in osteosarcoma. Through western blot analysis of AKT/mTOR pathway related proteins, we found that miR-451a inhibits the AKT/mTOR signaling pathway via PDPK1 which was previously reported as a potential diagnostic biomarker for osteosarcoma [30] and a tumor-propeller in osteosarcoma [24] . Further, we uncovered that miR-451a suppresses the AKT/mTOR signaling pathway via PDPK1-induced phosphorylation of AKT at Thr308 site through q-PCR analysis, Co-IP assay and in vitro phosphorylation experiment.…”

Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

“…It is a precursor of amyloid beta that contributes to producing amyloid plaques found in the brains of Alzheimer’s disease patients. APP is also reported as one of the diagnostic biomarkers for OS ( Zhang and Yang, 2018 ), and its high expression reduces the survival of OS patients but not pan-cancer patients. Taken together, APP can be a druggable target, selective to OS, and PCOLCE is one of its biological blockers.…”