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大规模转录组分析确定RNA甲基化调节因子为肺腺癌新的预后标志物。

Large-scale transcriptome analysis identified RNA methylation regulators as novel prognostic signatures for lung adenocarcinoma.

作者信息

Sun Lei, Liu Wen-Ke, Du Xiao-Wei, Liu Xiang-Li, Li Gao, Yao Yao, Han Tao, Li Wen-Ya, Gu Jia

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Oncology, General Hospital of Northern Theater Command, Shenyang, China.

出版信息

Ann Transl Med. 2020 Jun;8(12):751. doi: 10.21037/atm-20-3744.

Abstract

BACKGROUND

The abnormal expression of genes is an essential factor affecting the prognosis of cancer. RNA modification is a way of regulating post-transcriptional levels, including mA, mC, mA RNA methylation. Studies have found that RNA methylation regulates tumorigenesis development and stem cell regeneration. However, there are few studies on lung adenocarcinoma. This study aims to explore the clinical value of RNA methylation for lung adenocarcinoma.

METHODS

We summarized thirty-one RNA methylation regulators. The training set was obtained from The Cancer Genome Atlas (TCGA) database, and the test set was obtained from the Gene Expression Omnibus (GEO) database. The Wilcoxon test was used to analyze the expression of RNA methylation regulators. We constructed tumor subgroup models and risk models based on the expression of those regulators. Principal component analysis (PCA) and the receiver operating characteristic (ROC) confirmed the accuracy of the models. Real-time polymerase chain reaction (PCR) validates the results .

RESULTS

Most RNA methylation regulators had distinct expressions in tumor tissues and adjacent tissues (P<0.05). All the models showed high predictive performance (AUC: 0.65-0.82), and the five-year survival of patients in each group was statistically different (P<0.05). The patients in the high-risk group were more likely to have a higher stage, more lymph node metastases, and distant metastases, showing a poor clinical outcome. Patients with high expression of NOP2 or HNRNP were more likely to have a poorly differentiated experiment.

CONCLUSIONS

With our study, we found that the expressions of most RNA methylation regulators were significantly different in cancer and para-cancerous tissues. Different molecular phenotypes constructed by RNA methylation regulators can be independent risk factors for the prognosis of lung adenocarcinoma. Our study demonstrates the critical role of RNA methylation in lung adenocarcinoma, and it is expected to supply a reference for the prognostic stratification and treatment strategy development of lung adenocarcinoma.

摘要

背景

基因的异常表达是影响癌症预后的重要因素。RNA修饰是一种转录后水平的调控方式,包括m⁶A、m⁵C、m¹A RNA甲基化。研究发现,RNA甲基化调控肿瘤发生发展及干细胞再生。然而,关于肺腺癌的研究较少。本研究旨在探讨RNA甲基化对肺腺癌的临床价值。

方法

我们总结了31种RNA甲基化调节因子。训练集来自癌症基因组图谱(TCGA)数据库,测试集来自基因表达综合数据库(GEO)。采用Wilcoxon检验分析RNA甲基化调节因子的表达。我们基于这些调节因子的表达构建了肿瘤亚组模型和风险模型。主成分分析(PCA)和受试者工作特征(ROC)曲线证实了模型的准确性。实时聚合酶链反应(PCR)验证了结果。

结果

大多数RNA甲基化调节因子在肿瘤组织和癌旁组织中表达明显不同(P<0.05)。所有模型均显示出较高的预测性能(AUC:0.65 - 0.82),且每组患者的五年生存率有统计学差异(P<0.05)。高危组患者更可能处于更高分期、有更多淋巴结转移和远处转移,临床结局较差。NOP2或HNRNP高表达的患者更可能分化差。

结论

通过本研究,我们发现大多数RNA甲基化调节因子在癌组织和癌旁组织中的表达存在显著差异。由RNA甲基化调节因子构建的不同分子表型可作为肺腺癌预后的独立危险因素。我们的研究证明了RNA甲基化在肺腺癌中的关键作用,有望为肺腺癌的预后分层和治疗策略制定提供参考。

需注意,原文中“mA, mC, mA RNA methylation”可能有误,推测应为“m⁶A, m⁵C, m¹A RNA methylation”,译文已按此推测翻译。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd7c/7333141/36c8051cc26c/atm-08-12-751-f1.jpg

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