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肺鳞状细胞癌中m6A相关基因的预后作用及突变特征的综合分析

Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma.

作者信息

Gu Chang, Shi Xin, Qiu Wenli, Huang Zhenyu, Yu Yan, Shen Feng, Chen Yumei, Pan Xufeng

机构信息

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Front Cell Dev Biol. 2021 Mar 25;9:661792. doi: 10.3389/fcell.2021.661792. eCollection 2021.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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 ( < 0.05). Besides, METTL14 and ZC3H13 or YTHDF3 also had significant co-occurrence frequency ( < 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.

CONCLUSION

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.

摘要

背景

肺鳞状细胞癌(LUSC)的治疗方法有限。与m6A相关的基因可能是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。

方法

从癌症基因组图谱数据库中提取LUSC基因表达数据、突变数据及相应临床信息。鉴定差异表达基因(DEG),并探索LUSC患者的突变特征。然后,提取与m6A相关的基因并检测基因间的相关性。最后,研究这些基因的预后作用并建立列线图模型。此外,利用蛋白质-蛋白质相互作用(PPI)网络探索基因间的潜在相互作用。

结果

本研究共纳入551例LUSC样本,分别包含502例LUSC肿瘤样本和49例相邻正常LUSC样本。进一步探索了2970个上调的DEG和1806个下调的DEG。IGF2BP1和RBM15具有显著的共现频率(<0.05)。此外,METTL14与ZC3H13或YTHDF3也具有显著的共现频率(<0.05)。所有与m6A相关的基因均呈正相关。WTAP在TCGA数据库中被鉴定为预后基因,而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总生存期的显著预后因素。

结论

我们研究了LUSC患者的表达模式和突变特征,并鉴定出三个潜在的独立预后m6A相关基因(WTAP、YTHDC1和YTHDF1)用于LUSC患者的总生存期预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6555/8027321/b62a3ea7783f/fcell-09-661792-g001.jpg

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