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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00697

Cross-species gene expression analysis reveals gene modules implicated in human osteosarcoma

 Zheng Jin1, Shanshan Liu1, Pei Zhu1, Mengyan Tang1, Yuanxin Wang1, Yuan Tian2,  Dong Li1, Xun Zhu1, Dongmei Yan1* and  Zhenhua Zhu3*
  • 1Department of Immunology, College of Basic Medical Sciences, Jilin University, China
  • 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, China
  • 3Department of Orthopaedic Trauma, The First Hospital of Jilin University, China

Background: Osteosarcoma (OS) is one of the malignant bone tumors occurring in both human and canine, and in both of them, it is characterized by a high rate of metastasis and poor prognosis. Cross-species analysis reveals previously neglected molecular or signaling pathways involved in the progression of diseases and dogs are genetically comparable to humans and live in similar environments. Therefore, the aim of this study was to find out OS hub genes through a cross-species analysis.
Materials & Methods: All the human and canine OS gene expression data obtained by the Affymetrix platform were collected. After quality assessment and normalization, co-expression network was performed using weight gene co-expression network analysis (WGCNA). Species specific modules and consensus modules were identified. Protein-protein interaction (PPI) networks analysis was performed based on consensus gene modules. Then, consensus modules were functionally annotated and correlated with clinical traits. Hub nodes were identified by a subnetwork analysis of PPI network and WGCNA module membership. Modules of interest and hub nodes were validated in an external dataset.
Results: Three modules for the human network, 7 modules for the canine network and 4 consensus modules were identified. The consensus module 3 (C3) showed a significant correlation with the metastatic status in the training dataset and a significant correlation with metastasis free survival in the external dataset. Cluster of differentiation 86 (CD86) was identified as the hub gene of C3, showing a significant correlation with metastasis free survival.
Conclusion: Genes in C3 play an important role in OS metastasis, while CD86 might be a potential molecular biomarker for OS metastasis.

Keywords: Osteosarcoma, hub-genes, Cross-species analysis, WGCNA, CD86

Received: 09 Apr 2019; Accepted: 03 Jul 2019.

Edited by:

Zhixiang LU, Harvard Medical School, United States

Reviewed by:

Ruijiao Xin, Children's Hospital of Philadelphia, United States
Yi Peng, Northwestern Medicine, United States
LEI SHI, Salk Institute for Biological Studies, United States  

Copyright: © 2019 Jin, Liu, Zhu, Tang, Wang, Tian, Li, Zhu, Yan and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Dongmei Yan, Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, China, dmyan@jlu.edu.cn
Mr. Zhenhua Zhu, Department of Orthopaedic Trauma, The First Hospital of Jilin University, Changchun, Jilin Province, China, zhuzhenhua93@hotmail.com