| 骨肉瘤lncRNA的预后模型构建及实验验证 |
| Prognostic model construction and experimental validation of osteosarcoma lncRNA |
| 投稿时间：2025-04-02 |
| DOI：10.3969/j.issn.1672-5972.2025.06.003 |
| 中文关键词: 生物信息学 长链非编码RNA 骨肉瘤 预后模型 |
| 英文关键词:Bioinformatics Long-non coding RNA Osteosarcoma Prognostic model |
| 基金项目:国家自然科学基金项目（82360939）；国家自然科学基金项目（82460936） |
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| 中文摘要: |
| 目的 通过构建骨肉瘤（osteosarcoma, OS）中的长链非编码RNA（long-non coding RNA, lncRNA）预后模型，以探讨lncRNA在OS预后中的作用。方法 从公共数据库GTEx、Target中下载正常人的样本和OS患者的样本，通过使用perl脚本提取了样本中的lncRNA，使用差异分析得出了差异lncRNA，使用单因素Cox分析、最小绝对收缩选择算子（least absolute shrinkage and selection operator, LASSO）构建了OS的lncRNA风险预后模型。通过生存分析、风险列线图、校准曲线来验证模型的预测能力。为进一步研究预后模型中肿瘤微环境、免疫浸润、药物敏感性之间的关系，将筛选得到的6条lncRNA进行了实时荧光定量聚合酶链式反应（qRT-PCR）验证预后模型的可靠性。结果 ①成功构建了包含6个lncRNA（MIR133A1HG、MIR1-1HG、LINC02475、LINC00963、LINC00511、AP000873.2）的预后模型。列线图揭示该预后模型下OS患者的预后，校准曲线表明预测模型具有良好的预测能力。②免疫浸润分析低风险组提示B细胞、树突状细胞、辅助性T细胞、Th2细胞有更高的浸润水平，免疫检查点提示CD44、TNFSF4、HAVCR2、ADORA2A存在差异。药物敏感性分析提示对伏立诺他、星形孢菌素敏感。③生存分析揭示了低风险组具有更长的总生存期。qRT-PCR实验结果表明MIR133A1HG、MIR1-1HG在骨肉瘤细胞中呈低表达，LINC00963、LINC00511在骨肉瘤细胞中呈高表达，而LINC02475在骨肉瘤与正常细胞中表达无差异。结论 本研究构建的lncRNA预后模型能对OS患者的预后进行一个有效的预测，为OS的治疗提供更多的可行性。 |
| 英文摘要: |
| Objective To explore the role of long non-coding RNAs (lncRNAs) in the prognosis of osteosarcoma (OS) by constructing an lncRNA prognostic model.Methods Samples from normal individuals and OS patients were downloaded from the public databases GTEx and Target. The lncRNA in the samples was extracted by using the perl script, and the differential lncRNA was obtained by using the difference analysis. The lncRNA risk prognosis model of OS was constructed by using single factor Cox analysis and least absolute shrinkage and selection operator (LASSO). The predictive ability of the model was verified by survival analysis, risk nomogram and calibration curve. In order to further study the relationship between tumor microenvironment, immune infiltration and drug sensitivity in the prognostic model, 6 lncRNAs were detected by qRT-PCR to verify the reliability of the prognostic model.Results ①A prognostic model containing six lncRNAs (MIR133A1HG, MIR1-1HG, LINC02475, LINC00963, LINC00511, and AP000873.2) was successfully constructed. The nomogram revealed the prognosis of OS patients under the prognostic model, and the calibration curve showed that the prediction model had good predictive ability. ②Immune infiltration analysis showed that B cells, dendritic cells, helper T cells, and Th2 cells had higher infiltration levels, and immune checkpoints showed differences in CD44, TNFSF4, HAVCR2, and ADORA2A. Drug susceptibility analysis showed sensitivity to vorinostat and staurosporine. ③Survival analysis revealed that the low-risk group had longer overall survival. qRT-PCR experiments showed that MIR133A1HG and MIR1-1HG were expressed at low levels in osteosarcoma cells and at high levels in osteosarcoma cells. There was no difference in the expression of LINC02475 between osteosarcoma and normal cells, and LINC00963 and LINC00511 were expressed at high levels in osteosarcoma cells.Conclusion The lncRNA prognostic model constructed in this study can effectively predict the prognosis of OS patients and improve the feasibility of OS treatment. |
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