Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis.

Jianye Tan,Zhengwei Liu,Lijun Lin,Lutao Li,Shuang Zhu,Weizhong Qi,Sijing Li,Lin Li,Bingsheng Yang,Guofeng Wu,Haofeng Liang

doi:10.1155/2021/6646459

Jianye Tan, Zhengwei Liu + Show 9 more

Open Access

https://doi.org/10.1155/2021/6646459

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Journal: Journal of oncology	Publication Date: Jan 30, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Zhujiang Hospital

Abstract

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

Highlights

Osteosarcoma (OS) is characterized by a high recurrence rate and early lung metastasis
LncRNAs attract miRNAs, which block the interaction between miRNAs and messenger RNA (mRNA) [13]. is cascade of events affects mRNA expression and influences various human disease processes, including OS metastasis [13,14,15]
We show that transcriptions factors (TFs) regulate the expression of specific genes and signaling pathways, which define the fate of many cells. ese new molecular dynamics may explain the mechanism of OS metastasis

Summary

Introduction

Osteosarcoma (OS) is characterized by a high recurrence rate and early lung metastasis. It is more prevalent in children and adolescents and is the leading cause of poor survival rates [1]. E high mortality rate is associated with the lack of research on the mechanism related to metastatic. Due to its potential biomarker or therapeutic target, the ceRNA network has attracted enormous research interest for clinical application [8, 9]. Research on the ceRNA network and disease metastasis is of Journal of Oncology particular interest [10,11,12]. LncRNAs attract miRNAs, which block the interaction between miRNAs and mRNA [13]. is cascade of events affects mRNA expression and influences various human disease processes, including OS metastasis [13,14,15]

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