Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma.
Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma.
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DOI：
10.3389/fcell.2021.661792
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发表时间：
2021
影响因子：
5.5
通讯作者：
Pan X
中科院分区：
文献类型：
--
作者：
Gu C;Shi X;Qiu W;Huang Z;Yu Y;Shen F;Chen Y;Pan X
肺鳞状细胞癌（LUSC）的治疗方法有限。m6a相关基因可能是LUSC的下一个治疗靶点。在本研究中，我们探讨了m6a相关基因在LUSC中的预后作用和突变特征。从The Cancer Genome Atlas数据库中提取LUSC基因表达数据、突变数据以及相应的临床信息。鉴定差异表达基因（DEGs），探讨LUSC患者的突变特征。然后提取m6a相关基因，检测基因间的相关性。最后，研究了基因的预后作用，并建立了nomogram模型。此外，利用蛋白-蛋白相互作用（PPI）网络来探索基因之间潜在的相互作用。本研究共纳入551例LUSC样本，其中LUSC肿瘤样本502例，相邻正常LUSC样本49例。共发现2970个上调的deg和1806个下调的deg。IGF2BP1与RBM15共现频率显著（p < 0.05）。此外，METTL14与ZC3H13或YTHDF3也有显著的共现频率（p < 0.05）。所有m6a相关基因均为正相关。在TCGA数据库中，WTAP被鉴定为预后基因，YTHDC1和YTHDF1被鉴定为预后基因。在多因素Cox分析中，YTHDF1、年龄、pN分期、pTNM分期和吸烟均被确定为OS的重要预后因素。我们研究了LUSC患者的表达模式和突变特征，并确定了三个潜在的独立预后m6a相关基因（WTAP， YTHDC1和YTHDF1）与LUSC患者OS有关。
There have been limited treatment therapies for lung squamous cell carcinoma (LUSC). M6A-related genes may be the next therapeutic targets for LUSC. In this study, we explored the prognostic role and mutational characteristics of m6A-related genes in LUSC. LUSC gene expression data, mutational data, and corresponding clinical information were extracted from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified, and the mutation characteristics of LUSC patients were explored. Then, m6A-related genes were extracted and the correlations among the genes were detected. Finally, the prognostic roles of the genes were investigated and the nomogram model was developed. Besides, the protein–protein interaction (PPI) network was used to explore the potential interactions among the genes. In total, there are 551 LUSC samples enrolled in our study, containing 502 LUSC tumor samples and 49 adjacent normal LUSC samples, respectively. There were 2970 upregulated DEGs and 1806 downregulated DEGs were further explored. IGF2BP1 and RBM15 had significant co-occurrence frequency (p < 0.05). Besides, METTL14 and ZC3H13 or YTHDF3 also had significant co-occurrence frequency (p < 0.05). All the m6A-related genes represent the positive correlation. WTAP was identified as a prognostic gene in the TCGA database while YTHDC1 and YTHDF1 were identified as prognostic genes. In multivariate Cox analysis, YTHDF1, age, pN stage, pTNM stage, and smoking were all identified as significant prognostic factors for OS. We investigated the expression patterns and mutational characteristics of LUSC patients and identified three potential independent prognostic m6A-related genes (WTAP, YTHDC1, and YTHDF1) for OS in LUSC patients.
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