Construction of a Novel Prognostic Model in Lung Adenocarcinoma Based on 7-Methylguanosine-Related Gene Signatures.
Construction of a Novel Prognostic Model in Lung Adenocarcinoma Based on 7-Methylguanosine-Related Gene Signatures.
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基于 7-甲基鸟苷相关基因特征的肺腺癌新型预后模型的构建
DOI：
10.3389/fonc.2022.876360
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的证据表明，7-甲基鸟苷（m7 G）的修饰，一种RNA修饰，在肿瘤的进展。然而，迄今为止还没有全面的分析总结了m7 G相关基因标签在肺腺癌（LUAD）中的预测作用。在此，我们的目的是开发一种新的预测模型在LUAD的基础上m7 G相关的基因签名。LUAD转录组分析数据和相应的临床数据从癌症基因组图谱（TCGA）和两个基因表达综合数据集获得。经过筛选，我们首先获得了29个m7 G相关基因，其中大部分在肿瘤组织中上调，与总生存期（OS）呈负相关。根据m7 G相关基因的表达相似性，将来自TCGA-LUAD和GSE 68465数据集的组合样本进一步分为两个具有不同OS率和遗传异质性的聚类。然后，我们构建了一个新的预测模型，涉及四个基因，使用130个差异表达的基因在两个集群。将合并的样本以1：1的比例随机分为训练队列和内部验证队列，并将GSE 72094数据集用作外部验证队列。样本被分为高风险组和低风险组。我们证明，较高的风险评分是一个独立的负性预后因素，并预测OS差。进一步构建诺模图，以更好地预测LUAD患者的生存。功能富集分析表明，细胞周期和DNA复制相关的生物过程和途径在高危组中富集。更重要的是，低风险组大多数免疫细胞的浸润和富集程度更高，ESTIMATE、免疫和基质评分也更高。此外，高风险组的TIDE评分较低，大多数免疫检查点相关基因的表达较高。我们最后注意到，高风险组的患者对LUAD中常用的化疗药物更敏感。总之，我们在此首次总结了m7 G相关基因在LUAD中的改变和预后作用，然后构建了一个基于m7 G相关基因特征的预后模型，该模型可以准确稳定地预测LUAD患者的生存率，并指导个体化治疗决策。
Increasing evidence has implicated the modification of 7-methylguanosine (m7G), a type of RNA modification, in tumor progression. However, no comprehensive analysis to date has summarized the predicted role of m7G-related gene signatures in lung adenocarcinoma (LUAD). Herein, we aimed to develop a novel prognostic model in LUAD based on m7G-related gene signatures. The LUAD transcriptome profiling data and corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus datasets. After screening, we first obtained 29 m7G-related genes, most of which were upregulated in tumor tissues and negatively associated with overall survival (OS). According to the expression similarity of m7G-related genes, the combined samples from the TCGA-LUAD and GSE68465 datasets were further classified as two clusters that exhibit distinct OS rates and genetic heterogeneity. Then, we constructed a novel prognostic model involving four genes by using 130 differentially expressed genes among the two clusters. The combined samples were randomly divided into a training cohort and an internal validation cohort in a 1:1 ratio, and the GSE72094 dataset was used as an external validation cohort. The samples were divided into high- and low-risk groups. We demonstrated that a higher risk score was an independent negative prognostic factor and predicted poor OS. A nomogram was further constructed to better predict the survival of LUAD patients. Functional enrichment analyses indicated that cell cycle and DNA replication-related biological processes and pathways were enriched in the high-risk group. More importantly, the low-risk group had greater infiltration and enrichment of most immune cells, as well as higher ESTIMATE, immune, and stromal scores. In addition, the high-risk group had a lower TIDE score and higher expressions of most immune checkpoint-related genes. We finally noticed that patients in the high-risk group were more sensitive to chemotherapeutic agents commonly used in LUAD. In conclusion, we herein summarized for the first time the alterations and prognostic role of m7G-related genes in LUAD and then constructed a prognostic model based on m7G-related gene signatures that could accurately and stably predict survival and guide individualized treatment decision-making in LUAD patients.
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DOI：
10.2183/pjab.91.394
发表时间：
2015
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Furuichi Y
通讯作者：
Furuichi Y
影响因子：
4
作者：
Chen H;Ge XL;Zhang ZY;Liu M;Wu RY;Zhang XF;Xu LP;Cheng HY;Sun XC;Zhu HC
通讯作者：
Zhu HC
影响因子：
14.9
作者：
Boccaletto P;Stefaniak F;Ray A;Cappannini A;Mukherjee S;Purta E;Kurkowska M;Shirvanizadeh N;Destefanis E;Groza P;Avşar G;Romitelli A;Pir P;Dassi E;Conticello SG;Aguilo F;Bujnicki JM
通讯作者：
Bujnicki JM
影响因子：
7.7
作者：
Lahr, Roni M.;Fonseca, Bruno D.;Berman, Andrea J.
通讯作者：
Berman, Andrea J.
DOI：
10.1016/s0140-6736(17)33326-3
发表时间：
2018-03-17
期刊：
Lancet (London, England)
影响因子：
--
作者：
Allemani C;Matsuda T;Di Carlo V;Harewood R;Matz M;Nikšić M;Bonaventure A;Valkov M;Johnson CJ;Estève J;Ogunbiyi OJ;Azevedo E Silva G;Chen WQ;Eser S;Engholm G;Stiller CA;Monnereau A;Woods RR;Visser O;Lim GH;Aitken J;Weir HK;Coleman MP;CONCORD Working Group
通讯作者：
CONCORD Working Group