骨肉瘤铁死亡相关非编码RNA基因预测及免疫浸润

A ferroptosis-associated lncRNA genes-based prediction and immune infiltration in osteosarcoma

摘要:

[目的]探讨预测铁死亡相关 lncRNA，并构建骨肉瘤（osteosarcoma, OS）预后预测模型及其竞争性內源 RNA（com- peting endogenouse RNA, ceRNA） 调控网络。[方法] 从大型数据库 TARGET 下载高通量测序数据及对应的临床数据。运用 R 软件过滤低丰度基因并整理对应的临床信息后获得 85 例测序数据，提取 lncRNA 和 FRGs。基因本体论（GO）功能和京都基因和基因组百科全书 （KEGG） 通路富集分析。对最终筛选得到的 lncRNA、miRNA 以及 FRGs 基因进行 Spearman 相关性分析。 [结果] 从 TARGET-OS 数据集中提取到 7 658 个 lncRNA 和 175 个 FRGs，得到了 1 158 个与铁死亡显著相关的 lncRNA。GO 分析结果表明，CC 主要包括细胞外基质组织、成骨、细胞-基质粘附、受体介导的内吞作用；BP 主要包括细胞-基底连接、黏着斑、含胶原蛋白的细胞外基质、细胞接触前缘、游离核糖体。发现 lncRNA PVT1 与 miRNA （hsa-miR-106a-5p, hsa-miR17-5p, hsa-miR-20a-5p） 有确定结合靶点，进一步分析发现，lncRNA PVT1 基因与 OS 免疫有关 （R=-0.27, P=0.014）。高风险组 PDCD1LG2 和 CD27 表达量低于低风险组 （T-test, P＜0.05）。[结论] 铁死亡相关 lncRNA 预后模型具有较好的预测能力，为优化 OS 的管理提供了依据。铁死亡相关 lncRNA ceRNA 网络，可能为 OS 发生发展的分子机制提供有价值的数据支持。

Abstract:

[Objective] To explore the prognostic model of IncRNA for osteosarcoma (OS), and create competing endogenouse RNA (ceRNA) regulatory networks. [Methods] High- throughput sequencing data and corresponding clinical data were downloaded from the TARGET database after R software was used to filter low-abundance genes and collate corresponding clinical information, sequencing data of 85 cases were obtained, and lncRNA and FRGs were extracted. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Ge- nomes (KEGG) pathway enrichment analysis were conducted and the lncRNA, miRNA and FRGs genes were finally screened by Spearman correlation analysis. [Results] A total of 7 658 lncRNA and 175 FRGs were extracted from the TARGET-OS database and 1 158 lncRNAs were significantly associated with ferroptosis. GO analysis showed that CC mainly involved extracellular matrix, osteogenesis, cell-matrix adhesion and receptor-mediated endocytosis, while BP mainly involved cell-base junction, adhesion plaque, extracellular matrix contain- ing collagen, cell contact front and free ribosome. lncRNA PVT1 was found to have certain binding targets with miRNA (hsa-miR-106a5p, hsa-miR-17-5p, hsa-miR-20a-5p). Further analysis showed that lncRNA PVT1 gene was associated with OS immunity (R=-0.27, P= 0.014). The expressions of PDCD1LG2 and CD27 in high-risk group were lower than those in low-risk group (T-test, P＜0.05). [Conclu- sion] The prognosis model of lncRNA related to ferroptosis has good predictive ability, which provides a basis for optimizing the manage- ment of OS. lncRNA ceRNA networks related to ferroptosis may provide valuable data support for the molecular mechanism of OS occur- rence and development.