Department of Orthopedic surgery, Daping Hospital, Army medical university, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
Department of Radiation Oncology, Chongqing University Cancer Hospital, No. 181, Hanyu road, Shapingba District, Chongqing, 400030, PR China.
Hereditas. 2020 Jul 14;157(1):29. doi: 10.1186/s41065-020-00142-0.
The aim of this study is to identify the potential pathogenic and metastasis-related differentially expressed genes (DEGs) in osteosarcoma through bioinformatic analysis of Gene Expression Omnibus (GEO) database.
Gene expression profiles of GSE14359, GSE16088, and GSE33383, in total 112 osteosarcoma tissue samples and 7 osteoblasts, were analyzed. Seventy-four normal-primary DEGs (NPDEGs) and 764 primary-metastatic DEGs (PMDEGs) were screened. VAMP8, A2M, HLA-DRA, SPARCL1, HLA-DQA1, APOC1 and AQP1 were identified continuously upregulating during the oncogenesis and metastasis of osteosarcoma. The enriched functions and pathways of NPDEGs include procession and presentation of antigens, activation of MHC class II receptors and phagocytosis. The enriched functions and pathways of PMDEGs include mitotic nuclear division, cell adhesion molecules (CAMs) and focal adhesion. With protein-protein interaction (PPI) network analyzed by Molecular Complex Detection (MCODE) plug-in of Cytoscape software, one hub NPDEG (HLA-DRA) and 7 hub PMDEGs (CDK1, CDK20, CCNB1, MTIF2, MRPS7, VEGFA and EGF) were eventually selected, and the most significant pathways in NPDEGs module and PMDEGs module were enriched in the procession and presentation of exogenous peptide antigen via MHC class II and the nuclear division, respectively.
By integrated bioinformatic analysis, numerous DEGs related to osteosarcoma were screened, and the hub DEGs identified in this study are possibly part of the potential biomarkers for osteosarcoma. However, further experimental studies are still necessary to elucidate the biological function and mechanism of these genes.
本研究旨在通过对基因表达综合数据库（GEO）的生物信息学分析，鉴定骨肉瘤中潜在的致病和转移相关差异表达基因（DEGs）。
对 GSE14359、GSE16088 和 GSE33383 三个数据集共 112 例骨肉瘤组织样本和 7 例成骨细胞的基因表达谱进行了分析。筛选出 74 个正常原发 DEGs（NPDEGs）和 764 个原发转移 DEGs（PMDEGs）。VAMP8、A2M、HLA-DRA、SPARCL1、HLA-DQA1、APOC1 和 AQP1 被鉴定为在骨肉瘤的发生和转移过程中持续上调。NPDEGs 的富集功能和通路包括抗原的加工和呈递、MHC Ⅱ类受体的激活和吞噬作用。PMDEGs 的富集功能和通路包括有丝分裂核分裂、细胞黏附分子（CAMs）和黏附斑。通过 Cytoscape 软件的 Molecular Complex Detection（MCODE）插件分析蛋白质-蛋白质相互作用（PPI）网络，最终选择了一个 NPDEG 枢纽基因（HLA-DRA）和 7 个 PMDEG 枢纽基因（CDK1、CDK20、CCNB1、MTIF2、MRPS7、VEGFA 和 EGF），并且在 NPDEGs 模块和 PMDEGs 模块中最显著的通路分别富集于外源性肽抗原通过 MHC Ⅱ类的加工和呈递以及核分裂过程。
通过综合生物信息学分析，筛选出与骨肉瘤相关的大量 DEGs，本研究中鉴定的枢纽 DEGs 可能是骨肉瘤潜在生物标志物的一部分。然而，仍需要进一步的实验研究来阐明这些基因的生物学功能和机制。
