Zhang Yingying, Liu Xin, Liu Liwen, Li Jianhao, Hu Qiuyue, Sun Ranran
Precision Medicine Center, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
Key Laboratory of Clinical Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
Med Sci Monit. 2020 Feb 22;26:e919644. doi: 10.12659/MSM.919644.
BACKGROUND Lung adenocarcinoma (LUAD) is the most common subtype of lung malignancy and is the leading cause of cancer-related mortalities worldwide. N6-methyladenosine (m6A), the most prevalent internal modification of mRNAs, plays crucial roles in regulating mRNA splicing, exportation, localization, translation, and stability. This study assessed the expression patterns and prognostic value of m6A-related genes in LUAD. MATERIAL AND METHODS The expression data of 509 LUAD samples and 20 normal samples were obtained from the Cancer Genome Atlas (TCGA) to determine the mRNA expression levels of m6A-related genomic targets. mRNA expression of 6 LUAD datasets was obtained from the Gene Expression Omnibus (GEO) repository. Subsequently, the Human Protein Atlas (HPA) and tissue microarray (TMA) cohort were used to verify the expression pattern of m6A-related genes at mRNA and protein level. The t test was used to analyze correlations between m6A-related genes and clinical features. Finally, survival analysis was performed to assess the prognostic value of m6A-related genes in LUAD patients. RESULTS We found that KIAA1429, RBM15, METTL3, HNRNPC, HNRNPA2B1, YTHDF1, and YTHDF2 were upregulated in TCGA-LUAD databases. The analysis of 7 GEO databases was consistent with the TCGA. YTHDF1 was overexpressed in LUAD patients and YTHDF2 was overexpressed in the great majority of cases. METTL3, YTHDF1, and YTHDF2 were associated with better OS and RFS. CONCLUSIONS m6A-related genes were differentially expressed in LUAD compared to matched normal patients. The m6A-related genes METTL3, YTHDF1, and YTHDF2 could serve as novel biomarkers for the prognosis of LUAD.
背景 肺腺癌（LUAD）是肺恶性肿瘤最常见的亚型，也是全球癌症相关死亡的主要原因。N6-甲基腺苷（m6A）是mRNA最普遍的内部修饰，在调节mRNA剪接、输出、定位、翻译和稳定性方面发挥着关键作用。本研究评估了m6A相关基因在LUAD中的表达模式和预后价值。
材料与方法 从癌症基因组图谱（TCGA）获得509例LUAD样本和20例正常样本的表达数据，以确定m6A相关基因组靶点的mRNA表达水平。从基因表达综合数据库（GEO）获得6个LUAD数据集的mRNA表达。随后，利用人类蛋白质图谱（HPA）和组织微阵列（TMA）队列在mRNA和蛋白质水平验证m6A相关基因的表达模式。采用t检验分析m6A相关基因与临床特征之间的相关性。最后，进行生存分析以评估m6A相关基因在LUAD患者中的预后价值。
结果 我们发现，在TCGA-LUAD数据库中，KIAA1429、RBM15、METTL3、HNRNPC、HNRNPA2B1、YTHDF1和YTHDF2上调。对7个GEO数据库的分析与TCGA一致。YTHDF1在LUAD患者中过表达，而YTHDF2在大多数病例中过表达。METTL3、YTHDF1和YTHDF2与更好的总生存期（OS）和无复发生存期（RFS）相关。
结论 与匹配的正常患者相比，m6A相关基因在LUAD中差异表达。m6A相关基因METTL3、YTHDF1和YTHDF2可作为LUAD预后的新型生物标志物。
