肺鳞癌中与生存相关的 N-腺苷甲基转移酶特征及其临床验证。

Survival-associated N-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification.

机构信息

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250117, China.

Department of Oncology, Jiujiang University Affiliated Hospital, Jiujiang, 332000, China.

出版信息

BMC Cancer. 2021 Nov 24;21(1):1265. doi: 10.1186/s12885-021-08939-6.

DOI:10.1186/s12885-021-08939-6

PMID:34814861

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8611943/

Abstract

BACKGROUND

N-methyladenine (mA) is the most common modification of mRNA and IncRNA in higher organisms. mA has been confirmed to be related to the formation and progression of tumors and mA-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of mA-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis.

METHODS

We integrated three mA writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the mA methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro.

RESULTS

The results of the study showed that the expression of the three mA methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression.

CONCLUSIONS

Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of mA methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma.

摘要

背景

N6-甲基腺嘌呤（mA）是高等生物中 mRNA 和 IncRNA 最常见的修饰物。mA 已被证实与肿瘤的发生和进展有关，mA 相关基因可以作为多种肿瘤的预后生物标志物。然而，目前还没有关于肺鳞状细胞癌的类似研究。本研究的主要目的是探讨 mA 相关基因在肺鳞状细胞癌组织中的差异表达及其与患者临床预后的关系。

方法

我们整合了三种催化 mRNA 分子腺嘌呤甲基化的 mA 写入器。训练集包括来自癌症基因组图谱（TCGA）数据库的 501 例 LUSC 患者，测试集包括来自基因表达综合数据库（GEO）数据库的 181 例 LUSC 患者。基于 mA 甲基转移酶基因的表达水平，我们建立了肿瘤亚群和风险预后模型，以量化风险指数和患者的长期预后，并通过主成分分析（PCA）和接收者操作特征（ROC）曲线分析进行验证。在手术过程中获得肺鳞状细胞癌组织标本后，采用免疫组织化学（IHC）在体外验证结果。

结果

研究结果表明，三种 mA 甲基转移酶在肿瘤组织和正常组织中的表达差异具有统计学意义（P<0.05）。基于 METTL3 基因表达的生存预后模型显示出更好的预测性能（AUC：0.706）。高风险和低风险组的患者在生存时间和 5 年及 10 年生存率方面存在显著差异。免疫组化结果显示，METTL3 表达较高的患者生存时间长于 METTL3 表达较低的患者。