Open Access

Abnormal DNA methylation may contribute to the progression of osteosarcoma

  • Authors:
    • Xiao‑Gang Chen
    • Liang Ma
    • Jia‑Xin Xu
  • View Affiliations

  • Published online on: October 25, 2017     https://doi.org/10.3892/mmr.2017.7869
  • Pages:193-199
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The identification of optimal methylation biomarkers to achieve maximum diagnostic ability remains a challenge. The present study aimed to elucidate the potential molecular mechanisms underlying osteosarcoma (OS) using DNA methylation analysis. Based on the GSE36002 dataset obtained from the Gene Expression Omnibus database, differentially methylated genes were extracted between patients with OS and controls using t‑tests. Subsequently, hierarchical clustering was performed to segregate the samples into two distinct clusters, OS and normal. Gene Ontology (GO) and pathway enrichment analyses for differentially methylated genes were performed using the Database for Annotation, Visualization and Integrated Discovery tool. A protein‑protein interaction (PPI) network was established, followed by hub gene identification. Using the cut‑off threshold of ≥0.2 average β‑value difference, 3,725 unique CpGs (2,862 genes) were identified to be differentially methylated between the OS and normal groups. Among these 2,862 genes, 510 genes were differentially hypermethylated and 2,352 were differentially hypomethylated. The differentially hypermethylated genes were primarily involved in 20 GO terms, and the top 3 terms were associated with potassium ion transport. For differentially hypomethylated genes, GO functions principally included passive transmembrane transporter activity, channel activity and metal ion transmembrane transporter activity. In addition, a total of 10 significant pathways were enriched by differentially hypomethylated genes; notably, neuroactive ligand‑receptor interaction was the most significant pathway. Based on a connectivity degree >90, 7 hub genes were selected from the PPI network, including neuromedin U (NMU; degree=103) and NMU receptor 1 (NMUR1; degree=103). Functional terms (potassium ion transport, transmembrane transporter activity, and neuroactive ligand‑receptor interaction) and hub genes (NMU and NMUR1) may serve as potential targets for the treatment and diagnosis of OS.

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January 2018
Volume 17 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Chen, X., Ma, L., & Xu, J. (2018). Abnormal DNA methylation may contribute to the progression of osteosarcoma. Molecular Medicine Reports, 17, 193-199. https://doi.org/10.3892/mmr.2017.7869
MLA
Chen, X., Ma, L., Xu, J."Abnormal DNA methylation may contribute to the progression of osteosarcoma". Molecular Medicine Reports 17.1 (2018): 193-199.
Chicago
Chen, X., Ma, L., Xu, J."Abnormal DNA methylation may contribute to the progression of osteosarcoma". Molecular Medicine Reports 17, no. 1 (2018): 193-199. https://doi.org/10.3892/mmr.2017.7869