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基于铁死亡相关的lncRNA在肺鳞癌预后的分析

Prognostic analysis based on ferroptosis related lncRNAs in lung squamous cell carcinoma

:113-120
 
目的 探究铁死亡相关的lncRNA在肺鳞状上皮细胞癌(简称肺鳞癌)患者中的预后意义。方法 从美国癌症和肿瘤基因图谱数据库(the Cancer Genome Atlas,TCGA)中下载肺鳞癌数据551例,包括49例正常对照样本和502例肺鳞癌患者样本。筛选出与铁死亡相关基因的共表达的lncRNA,使用单变量Cox回归进一步筛选lncRNA,然后,使用Lasso回归和多元Cox回归分构建铁死亡相关的lncRNA模型。建立基于模型的风险评分,并使用Cox回归测试其是否为独立的预后因素。铁死亡相关lncRNAs的功能富集使用基因本体(Gene Ontology)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)可视化。结果 4个预后铁死亡相关的lncRNA(AC253536.6,FLJ46906LUCAT,AC022150.2)显著不同,这构建了铁死亡相关的lncRNA模型。此模型将肺鳞癌患者分为低风险组和高风险组。基于模型的风险评分是肺鳞癌患者的显著独立因素(HR =2.116,95%CI=1.513~2.961;P<0.001)。此外,4个lncRNA在铁死亡过程,代谢和肿瘤经典途径中均显著富集。结论 4个铁死亡相关的lncRNAs可能是肺鳞癌患者的分子生物标志物和治疗靶标。
Objective To explore the prognostic significance of ferroptosis related lncRNAs in patients with lung squamous cell carcinoma. Methods Data of 551 lung squamous cell carcinoma cases was downloaded from the Cancer Genome Atlas (TCGA) of the United States, including 49 normal control samples and 502 lung squamous cell carcinoma samples. The lncRNAs co-expressed with genes related to ferroptosis was screened out. Univariate Cox regression was used to further screen out the lncRNAs. Then, Lasso regression and multiple Cox regression were used to construct lncRNA models related to ferroptosis. A model-based risk score system was established and Cox regression was used to test whether it was an independent prognostic factor. The functional enrichment of ferroptosis related lncRNAs were visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Results The four prognostic ferroptosis related lncRNAs (AC253536.6, FLJ46906 LUCAT, AC022150.2) were significantly different, and the ferroptosis lncRNAs model was constrncted with them. This model divided lung squamous cell carcinoma patients into low-risk group and high-risk group. The model-based risk score was a significant independent factor for patients with lung squamous cell carcinoma (HR=2.116, 95% CI=1.513-2.961; P<0.001). In addition, the four lncRNAs were significantly enriched in metabolism and tumor classical pathways during the ferroptosis process. Conclusions The four ferroptosis lncRNAs could be molecular biomarkers and therapeutic targets for patients with lung squamous cell carcinoma.
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