Identification of pathway-related modules in high-grade osteosarcoma based on topological centrality of network strategy.

OBJECTIVE

The objective of this paper is to identify pathway-related modules which are defined as in high-grade osteosarcoma based on topological centralities analysis of networks.

MATERIALS AND METHODS

Co-expression network was constructed by weighted gene co-expression network analysis (WGCNA) based on differentially expressed genes (DEGs). Pathway enrichment analysis was conducted by Kyoto Encyclopedia of Genes and Genomes (KEGG) database to detect pathway enriched genes. Pathway-related modules of pathway enriched genes were mined from the co-expression network. Then topological centralities (degree, closeness, stress and betweenness centrality) analyses for co-expression network and sub-networks were performed to explore hub genes. Validation of hub genes was carried out utilizing reverse transcription-polymerase chain reaction (RT-PCR) assays.

RESULTS

There were 129 nodes and 1229 edges in co-expression network. We obtained a total of 16 hub genes and 11 pathway-related modules. Module 17 (Bladder cancer module) was the most significant module, which comprising 9 of 16 hub genes and 6 pathway enriched genes, taking intersection elements (CAV1 and CCND1). RT-PCR results showed that both of CAV1 and CCND1 in high-grade osteosarcoma were significantly differentially expressed compared with normal controls.

CONCLUSIONS

This work may contribute to understanding the molecular pathogenesis and provide potential biomarkers for detections and effective therapies of high-grade osteosarcoma.