Zhang Jian, Huang Chi, Zhu Guiqi, He Guanyi, Xu Wenbo, Li Jianming, Wang Dong, Han Kecheng, Shen Zilong, Liu Jianyu
Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang, China.
Department of Rheumatology and Immunology, Zaozhuang Municipal Hospital, 277102 Shandong, China.
J Oncol. 2022 Mar 26;2022:8024979. doi: 10.1155/2022/8024979. eCollection 2022.
Osteosarcoma is the most common primary malignancy in the musculoskeletal system. It is reported that copy number variation- (CNV-) derived lncRNAs contribute to the progression of osteosarcoma. However, whether CNV-derived lncRNAs affect the prognosis of osteosarcoma remains unclear. Here, we obtained osteosarcoma-related CNV data and gene expression profiles from The Cancer Genome Atlas (TCGA) database. CNV landscape analysis indicated that copy number amplification of lncRNAs was more frequent than deletion in osteosarcoma samples. Thirty-four CNV-lncRNAs with DNA-CNV frequencies greater than 30% and their corresponding 294 mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses revealed that these mRNAs were mainly enriched in olfaction, olfactory receptor activity, and olfactory transduction processes. Furthermore, we predicted that a total of 23 genes were -regulated by 16 CNV-lncRNAs, while 30 transcription factors (TFs) were -regulated by 5 CNV-lncRNAs. Through -tests, univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO), we constructed a CNV-related risk model including 3 lncRNAs (AC129492.1, PSMB1, and AC037459.4). The Kaplan-Meier (K-M) curves indicated that patients with high-risk scores showed poor prognoses. The areas under the receiver operating characteristic (ROC) curves (AUC) for predicting 3-, 5-, and 7-year overall survival (OS) were greater than 0.7, showing a satisfactory predictive efficiency. Gene set enrichment analysis (GSEA) revealed that the prognostic signature was intimately linked to skeletal system development, immune regulation, and inflammatory response. Collectively, our study developed a novel 3-CNV-lncRNA prognostic signature that would provide theoretical guidance for the clinical prognostic management of osteosarcoma.
骨肉瘤是肌肉骨骼系统中最常见的原发性恶性肿瘤。据报道,拷贝数变异(CNV)衍生的长链非编码RNA(lncRNA)促进了骨肉瘤的进展。然而,CNV衍生的lncRNA是否影响骨肉瘤的预后仍不清楚。在此,我们从癌症基因组图谱(TCGA)数据库中获得了骨肉瘤相关的CNV数据和基因表达谱。CNV景观分析表明,在骨肉瘤样本中,lncRNA的拷贝数扩增比缺失更频繁。鉴定出34个DNA-CNV频率大于30%的CNV-lncRNA及其相应的294个mRNA。基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析表明,这些mRNA主要富集于嗅觉、嗅觉受体活性和嗅觉转导过程。此外,我们预测共有23个基因受16个CNV-lncRNA调控,而30个转录因子(TF)受5个CNV-lncRNA调控。通过检验、单变量Cox回归分析和最小绝对收缩和选择算子(LASSO),我们构建了一个包含3个lncRNA(AC129492.1、PSMB1和AC037459.4)的CNV相关风险模型。Kaplan-Meier(K-M)曲线表明,高风险评分的患者预后较差。预测3年、5年和7年总生存期(OS)的受试者工作特征(ROC)曲线下面积(AUC)大于0.7,显示出令人满意的预测效率。基因集富集分析(GSEA)表明,预后特征与骨骼系统发育、免疫调节和炎症反应密切相关。总的来说,我们的研究开发了一种新的3-CNV-lncRNA预后特征,这将为骨肉瘤的临床预后管理提供理论指导。