Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis

• Published in: International journal of molecular sciences Vol. 21; no. 3; p. 1053
• Main Authors: Cabrera-Andrade, Alejandro, López-Cortés, Andrés, Jaramillo-Koupermann, Gabriela, Paz-Y-Miño, César, Pérez-Castillo, Yunierkis, Munteanu, Cristian R, González-Díaz, Humbert, Pazos, Alejandro, Tejera, Eduardo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05-02-2020; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Bioinformatics; Biomedical materials; Bone cancer; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Cell cycle; communality analysis; Computational Biology - methods; Consensus; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; DNA Repair - genetics; early recognition; Etiology; Gelatinase A; Gelatinase B; Gene Expression Regulation, Neoplastic - genetics; Gene Ontology; gene prioritization; Gene Regulatory Networks - genetics; Genes; Humans; MAP kinase; Metabolism; Metastases; Methods; Molecular modelling; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - pathology; p53 Protein; Pathogenesis; Protein Interaction Maps - genetics; Proteins; Sarcoma; Signal processing; Signal Transduction - genetics; Tumors; early recognition; pathogenesis; gene prioritization; communality analysis; osteosarcoma
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21031053

Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein-protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as
and
, and genes associated with DNA repair complexes, like
,
,
, and
. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.