Abstract
The molecular mechanism of osteosarcoma (OS) based on protein-coding genes has largely been studied in the past decades. However, much remains to be explored when it comes to the role that long noncoding RNAs (lncRNAs) play in the pathogenesis and progression of OS and how they are associated with OS metastasis. In the present study, we collected RNA-seq-based gene expression data of 82 OS samples from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database, along with their clinical information. We found that 50 lncRNAs were significantly associated with patients' survival by univariable Cox regression model. Moreover, we built multivariable Cox regression model based on 7 lncRNAs and successfully stratified patients into two risk groups, which exhibited significantly different prognostic outcomes. Significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways detected by differential expression analysis on DEGs between the two groups with different prognostic outcomes were both immune-related, indicating that such GO terms and pathways are critical for OS survival. Among the seven lncRNA signatures, AC011442.1 was predicted to act as an oncogenic driver in OS by correlation analysis of copy number alteration (CNA) and lncRNA expression, and it was predicted to regulate AMPK and hedgehog signaling pathways. In summary, the identification of novel prognostic lncRNAs in OS could not only improved our understanding of the lncRNAs involved in OS tumorigenesis or progression but also assist the diagnosis and development of molecularly targeted therapies for OS, which in turn benefit patients' survival.
Highlights
Osteosarcoma (OS) is among the most prevalent malignancies in children and adolescents [1]
Based on the gene annotation from the Ensembl database and criteria regarding TPM, we selected 3,159 long noncoding RNA for later establishment of the prognostic risk model. Among these 3,159 long noncoding RNAs (lncRNAs), we identified 50 lncRNAs significantly associated with patients’ overall survival by univariable Cox regression model
These results indicated that the prognostic lncRNAs identified by the univariable Cox regression model may be essential for OS tumorigenesis and/or progression
Summary
Osteosarcoma (OS) is among the most prevalent malignancies in children and adolescents [1]. According to the American Cancer Society, the estimated number of newly diagnosed cases of skeletal malignancies in 2017 would reach 3,260 in the United States, among them there would be roughly over 600 OS patients [4]. No significant improvement in 10-year overall survival of OS patients has been observed since the 1990s [6]. The magical effect of traditional tumor resection surgery and chemotherapy seems to encounter a bottleneck as they had once improved overall 10-year survival of OS from 30% to about 50% in the 1970s, and with the advances in molecular biology and related techniques, molecularly targeted therapies have since emerged as a new option in the management strategy of various cancers, including OS
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