m6A调节因子在肺腺癌和肺鳞癌中的生物学差异

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摘要目的探讨m6A调节因子在肺腺癌(LUAD)和肺鳞癌(LUSC)中的生物学差异。方法在癌症基因组图谱(TCGA)数据库中获取LUAD和LUSC相关表达谱数据,并利用R分析26个m6A调节因子的潜在靶基因在LUAD和LUSC的肿瘤组织与正常组织之间的表达差异;利用癌症蛋白质组图谱(TCPA)的反相蛋白微阵列(RPPA)数据计算26个m6A调节因子在10个肿瘤相关通路的通路活性评分(PAS)与差异;利用 TCGA 数据库采用单因素Cox回归分析(Univariate COX analysis)和Kaplan-Meier 生存分析方法分析m6A调节因子的潜在靶基因对LUAD和LUSC患者预后的影响及差异。结果在26个m6A调节因子中,ZCCHC4、ALKBH1和YTHDF2仅在LUAD的肿瘤组织和正常组织中表达水平差异具有统计学意义,IGF2BP2和YTHDC2仅在LUSC的肿瘤组织和正常组织中表达水平差异具有统计学意义。m6A调节因子在LUAD和LUSC中,参与调控的通路活性存在明显的差异,METTL3、METTL5、METTL14、ZC3H13、RBMX和FTO仅在LUAD中的Apoptosis、Cell cycle、EMT和RAS/MAPK等肿瘤相关通路中发挥激活或抑制功能,EIF3A、YTHDC2和RBM15B仅在LUSC中的PI3K/AKT和TSC/mTOR信号通路中发挥抑制或激活作用。IGF2BP3和IGF2BP3调节因子的表达与LUAD预后生存呈负相关,与LUSC预后生存呈正相关。结论相同的m6A调节因子可能在LUAD和LUSC的生物学过程中发挥着不同的调控功能。

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	莘华
	刘智
	张洁莉

关键词 ：肺腺癌, 肺鳞癌, m6A, 差异表达, 通路活性, 预后

Abstract：Objective To compare the biological difference of m6A regulators in lung adenocarcinoma(LUAD) and lung squamous carcinoma(LUSC). Methods The expression profiles of LUAD and LUSC were obtained from the Cancer Genome Atlas (TCGA) database, and R was used to analyze the expression differences of 26 potential target genes of m6A regulators between LUAD and LUSC tumor tissues and normal tissues. The Cancer Proteome Atlas (TCPA) and Reverse phase protein array (RPPA) data were used to calculate the pathway activity scores (PAS) of the 26 m6Aregulators in 10 tumor-related pathways. Univariate COX analysis and Kaplan-Meier survival analysis were used to analyze the impact and difference of potential target genes of m6A regulators on prognosis of LUAD and LUSC patients. Results Among the 26 m6A regulators, the differences in the expression levels of ZCCHC4, ALKBH1 and YTHDF2 were statistically significant only in tumour and normal tissues in LUAD, and the differences in the expression levels of IGF2BP2 and YTHDC2 were statistically significant only in tumour and normal tissues in LUSC. In LUAD and LUSC, there were significant differences in the activity of the pathways involved in the regulation of m6A regulators. METTL3, METTL5, METTL14, ZC3H13, RBMX and FTO only played activating or inhibiting functions in tumour-related pathways such as Apoptosis, Cell cycle, EMT and RAS/MAPK in LUAD, while EIF3A, YTHDC2 and RBM15B only played inhibiting or activating roles in PI3K/AKT and TSC/mTOR signalling pathways in LUSC. The expression of IGF2BP3 and IGF2BP3 regulators was negatively correlated with prognostic survival in LUAD and positively correlated with prognostic survival in LUSC. Conclusions The same m6A regulators may play different regulatory roles in the biological processes of LUAD and LUSC.

Key words： lung adenocarcinoma lung squamous carcinoma m6A differential expression pathway activity prognosis

收稿日期: 2022-12-20

ZTFLH:

R734.2

通讯作者: 张洁莉,E-mail:baby88170@sina.com

作者简介: 莘华,本科学历,主治医师。

引用本文:

莘华, 刘智, 张洁莉. m6A调节因子在肺腺癌和肺鳞癌中的生物学差异[J]. 武警医学, 2023, 34(6): 494-500. XIN Hua, LIU Zhi, ZHANG Jieli. Biological difference of m6A regulators in lung adenocarcinoma and lung squamous carcinoma. Med. J. Chin. Peop. Armed Poli. Forc., 2023, 34(6): 494-500.

链接本文:

http://journal08.magtechjournal.com/Jwk_wjyx/CN/ 或 http://journal08.magtechjournal.com/Jwk_wjyx/CN/Y2023/V34/I6/494

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