PDF(Pubmed)
Abstract：
UNASSIGNED: Lung adenocarcinoma (LUAD) has become one of the most lethal cancers, for which the recurrence and survival rates remain unfavorable. The tumor necrosis factor (TNF) family is involved in tumorigenesis and tumor progression. Various long non-coding RNAs (lncRNAs) play important roles by mediating the TNF family in cancer. Therefore, this study aimed to construct a TNF-related lncRNA signature to predict prognosis and immunotherapy response in LUAD.
UNASSIGNED: The expression of TNF family members and their related lncRNAs in a total of 500 enrolled LUAD patients was collected from The Cancer Genome Atlas (TCGA). Univariate Cox and the least absolute shrinkage and selection operator (LASSO)-Cox analysis was used to construct a TNF family-related lncRNA prognostic signature. Kaplan-Meier (KM) survival analysis was used to evaluate survival status. The time-dependent area under the receiver operating characteristic (ROC) curve (AUC) values were used to assess the predictive value of the signature to 1-, 2-, and 3-year overall survival (OS). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to identify the signature-related biological pathways. Furthermore, tumor immune dysfunction and exclusion (TIDE) analysis was employed to evaluate immunotherapy response.
UNASSIGNED: A total of 8 TNF-related lncRNAs significantly associated with OS of LUAD patients were used to construct a TNF family-related lncRNA prognostic signature. According to risk score, these patients were divided into high- and low-risk subgroups. The KM survival analysis indicated that patients in the high-risk group showed significantly less favorable OS than that of low-risk group. The AUC values in predicting 1-, 2-, and 3-year OS were 0.740, 0.738, and 0.758, respectively. Moreover, the GO and KEGG pathway analyses demonstrated that these lncRNAs were closely involved in immune-related signaling pathways. The further TIDE analysis indicated that high-risk patients had a lower TIDE score than that of low-risk patients, indicating that high-risk patients may be appropriate candidates for immunotherapy.
UNASSIGNED: For the first time, this study constructed and validated a prognostic predictive signature of LUAD patients based on TNF-related lncRNAs, and the signature showed good performance to predict immunotherapy response. Therefore, this signature may provide new strategies for individualized treatment of LUAD patients.
UNASSIGNED: The expression of TNF family members and their related lncRNAs in a total of 500 enrolled LUAD patients was collected from The Cancer Genome Atlas (TCGA). Univariate Cox and the least absolute shrinkage and selection operator (LASSO)-Cox analysis was used to construct a TNF family-related lncRNA prognostic signature. Kaplan-Meier (KM) survival analysis was used to evaluate survival status. The time-dependent area under the receiver operating characteristic (ROC) curve (AUC) values were used to assess the predictive value of the signature to 1-, 2-, and 3-year overall survival (OS). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to identify the signature-related biological pathways. Furthermore, tumor immune dysfunction and exclusion (TIDE) analysis was employed to evaluate immunotherapy response.
UNASSIGNED: A total of 8 TNF-related lncRNAs significantly associated with OS of LUAD patients were used to construct a TNF family-related lncRNA prognostic signature. According to risk score, these patients were divided into high- and low-risk subgroups. The KM survival analysis indicated that patients in the high-risk group showed significantly less favorable OS than that of low-risk group. The AUC values in predicting 1-, 2-, and 3-year OS were 0.740, 0.738, and 0.758, respectively. Moreover, the GO and KEGG pathway analyses demonstrated that these lncRNAs were closely involved in immune-related signaling pathways. The further TIDE analysis indicated that high-risk patients had a lower TIDE score than that of low-risk patients, indicating that high-risk patients may be appropriate candidates for immunotherapy.
UNASSIGNED: For the first time, this study constructed and validated a prognostic predictive signature of LUAD patients based on TNF-related lncRNAs, and the signature showed good performance to predict immunotherapy response. Therefore, this signature may provide new strategies for individualized treatment of LUAD patients.
摘要：
■肺腺癌（LUAD）已成为最致命的癌症之一，复发率和生存率仍然不利。肿瘤坏死因子(TNF)家族参与肿瘤发生和肿瘤进展。各种长链非编码RNA（lncRNA）通过介导TNF家族在癌症中发挥重要作用。因此,本研究旨在构建一个与TNF相关的lncRNA特征来预测LUAD的预后和免疫治疗反应。
■从癌症基因组图谱(TCGA)收集总共500名登记的LUAD患者中TNF家族成员及其相关lncRNAs的表达。使用单变量Cox和最小绝对收缩和选择算子(LASSO)-Cox分析来构建TNF家族相关的lncRNA预后特征。Kaplan-Meier(KM)生存分析用于评估生存状态。受试者工作特征（ROC）曲线下的时间依赖性面积（AUC）值用于评估特征对1-，2-,和3年总生存期（OS）。应用基因本体论(GO)功能注释和京都基因和基因组百科全书(KEGG)途径分析来鉴定特征相关的生物学途径。此外，肿瘤免疫功能障碍和排斥(TIDE)分析用于评估免疫治疗反应.
■总共使用8种与LUAD患者OS显著相关的TNF相关lncRNA来构建TNF家族相关lncRNA预后特征。根据风险评分，这些患者分为高危和低危亚组.KM生存分析表明，高风险组患者的OS明显低于低风险组。预测1-的AUC值，2-,3年OS分别为0.740、0.738和0.758。此外，GO和KEGG通路分析表明,这些lncRNAs与免疫相关信号通路密切相关.进一步的TIDE分析表明，高风险患者的TIDE评分低于低风险患者，表明高危患者可能是免疫治疗的合适人选.
■第一次，这项研究基于TNF相关的lncRNAs构建并验证了LUAD患者的预后预测特征，和签名显示良好的性能，以预测免疫治疗反应。因此,这一特征可能为LUAD患者的个体化治疗提供新的策略.
■从癌症基因组图谱(TCGA)收集总共500名登记的LUAD患者中TNF家族成员及其相关lncRNAs的表达。使用单变量Cox和最小绝对收缩和选择算子(LASSO)-Cox分析来构建TNF家族相关的lncRNA预后特征。Kaplan-Meier(KM)生存分析用于评估生存状态。受试者工作特征（ROC）曲线下的时间依赖性面积（AUC）值用于评估特征对1-，2-,和3年总生存期（OS）。应用基因本体论(GO)功能注释和京都基因和基因组百科全书(KEGG)途径分析来鉴定特征相关的生物学途径。此外，肿瘤免疫功能障碍和排斥(TIDE)分析用于评估免疫治疗反应.
■总共使用8种与LUAD患者OS显著相关的TNF相关lncRNA来构建TNF家族相关lncRNA预后特征。根据风险评分，这些患者分为高危和低危亚组.KM生存分析表明，高风险组患者的OS明显低于低风险组。预测1-的AUC值，2-,3年OS分别为0.740、0.738和0.758。此外，GO和KEGG通路分析表明,这些lncRNAs与免疫相关信号通路密切相关.进一步的TIDE分析表明，高风险患者的TIDE评分低于低风险患者，表明高危患者可能是免疫治疗的合适人选.
■第一次，这项研究基于TNF相关的lncRNAs构建并验证了LUAD患者的预后预测特征，和签名显示良好的性能，以预测免疫治疗反应。因此,这一特征可能为LUAD患者的个体化治疗提供新的策略.
