The pathological tissue expression pattern and clinical significance of m6A-regulatory genes in non-small cell lung cancer
The pathological tissue expression pattern and clinical significance of m6A-regulatory genes in non-small cell lung cancer
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m6A调控基因在非小细胞肺癌的病理组织表达模式及临床意义
DOI：
10.1002/jgm.3397
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发表时间：
2021-12-01
影响因子：
3.5
通讯作者：
Huang, Yanming
中科院分区：
文献类型：
--
作者：
Li, Yujie;Zhang, Xin;Huang, Yanming
研究背景m6 A相关蛋白的异常表达与非小细胞肺癌（NSCLC）的发生、发展密切相关。目前的研究主要集中在单个m6 A调控基因及其作用机制上，多个m6 A调控蛋白在NSCLC中的表达尚不清楚。因此，有必要系统地检测这些蛋白质，特别是在临床标本中。方法应用生物信息学分析方法，利用美国癌症基因组图谱（TCGA）和AE-meta数据库，分析m6 A调控基因的表达及其与TP 53、EGFR和KRAS等常见基因突变的相关性。采用免疫组化方法检测61例良性肺组织和316例非小细胞肺癌组织中m6 A调节蛋白的表达。统计分析m6 A调节蛋白表达与肺癌患者临床病理特征、生存率和常见基因突变的相关性。结果使用TCGA和AE-meta数据库的信息分析13个核心m6 A调节因子的mRNA水平，显示与邻近正常组织相比，YTHDF 1在NSCLC中的水平上调。免疫组化结果显示，NSCLC组织中胃L3、ALKBH 5、YTHDC 2和YTHDF 1的表达明显上调。进一步的分析表明，差异表达的m6 A调节蛋白（包括YTHL 3、ALKBH 5、YTHDC 2和YTHDF 1）与非小细胞肺癌患者的不良临床病理特征和生存率之间存在正相关性。根据本研究入组的NSCLC患者的统计，EGFR外显子19突变患者的胃L3蛋白水平高于EGFR野生型患者。结论m6 A调节因子包括胃L3、ALKBH 5、YTHDC 2和YTHDF 1可作为NSCLC的预测指标，有助于NSCLC的早期发现和诊断。
Background Aberrant expression of m6A-related proteins contributes to the occurrence and progression of non-small cell lung cancer (NSCLC). Current studies mainly focus on single m6A regulatory genes and their underlying mechanisms, and the expression of multiple m6A regulatory proteins in NSCLC remains unclear. Therefore, it is necessary to systematically examine these proteins, particularly in clinical specimens. Methods Bioinformatic analysis was used to determine the expression of m6A regulatory genes and their correlation with common gene mutations, such as TP53, EGFR and KRAS, using The Cancer Genome Atlas (TCGA) and the AE-meta databases. Immunohistochemistry was employed to analyze the protein expression of m6A regulatory proteins in 61 benign lung tissues and 316 NSCLC tissues. Statistical analysis was performed to calculate the correlation between the expression of m6A regulatory proteins and clinicopathological features, survival, and common gene mutations in lung carcinoma patients. Results Analysis of the mRNA levels of 13 core m6A regulators, using information from TCGA and the AE-meta databases, revealed that YTHDF1 levels were upregulated in NSCLC compared to those in adjacent normal tissues. Immunohistochemical staining showed that the expression of METTL3, ALKBH5, YTHDC2 and YTHDF1 was significantly upregulated in NSCLC tissues. Further analyses demonstrated a positive correlation between differentially expressed m6A regulatory proteins, including METTL3, ALKBH5, YTHDC2 and YTHDF1, and the poor clinicopathological features and survival of NSCLC patients. According to the statistics of NSCLC patients enrolled in the present study, the protein levels of METTL3 in patients with EGFR exon-19 mutation were higher than those in patients with wild-type EGFR. Conclusions Our results indicate that m6A regulators, including METTL3, ALKBH5, YTHDC2 and YTHDF1, could serve as predictive markers of NSCLC, which will facilitate the early detection and diagnosis of NSCLC.