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泛癌症分析将 RNA mG 甲基转移酶表达的改变与致癌途径、免疫细胞浸润和总体生存联系起来。

Pan-Cancer Analysis Links Altered RNA mG Methyltransferase Expression to Oncogenic Pathways, Immune Cell Infiltrations and Overall Survival.

机构信息

Epigenetics and RNA Biology Laboratory, Charles Perkins Centre, University of Sydney, Camperdown, Australia.

Faculty of Medicine and Health, University of Sydney, Camperdown, Australia.

出版信息

Cancer Rep (Hoboken). 2024 Jul;7(7):e2138. doi: 10.1002/cnr2.2138.

Abstract

BACKGROUND

N7-methylguanosine (mG) modification is one of the most prevalent RNA modifications in humans. Dysregulated mG modifications caused by aberrant expression of mG writers contribute to cancer progression and result in worse patient survival in several human cancers. However, studies that systematically assess the frequency and clinical relevance of aberrant mG writer expression in a pan-cancer cohort remain to be performed.

AIMS

This study aims to systematically investigate the molecular alteration and clinical relevance of mG methyltransferase in human cancers.

METHODS

We analysed genome, transcriptome and clinical data from the Cancer Genome Atlas Research Network spanning 33 types of human cancers for aberrant changes in genes encoding mG writers.

RESULT

We demonstrate that mG writers are dysregulated in human cancers and are associated predominantly with poorer survival. By dividing patients into those with high and low mG scores, we show that a lower mG score is generally associated with immune infiltration and better response to immunotherapy.

CONCLUSION

Our analyses indicate the genetic alterations, expression patterns and clinical relevance of mG writers across various cancers. This study provides insights into the potential utility of mG writer expression as a cancer biomarker and proposes the possibility of targeting mG writers for cancer therapy.

摘要

背景

N7-甲基鸟苷(mG)修饰是人类最普遍的 RNA 修饰之一。mG 修饰的失调是由于 mG 写入器的异常表达引起的,这导致了几种人类癌症的进展,并导致患者的生存状况恶化。然而,系统评估 mG 写入器在泛癌队列中的异常表达频率和临床相关性的研究仍有待开展。

目的

本研究旨在系统研究 mG 甲基转移酶在人类癌症中的分子改变和临床相关性。

方法

我们分析了癌症基因组图谱研究网络的基因组、转录组和临床数据,涵盖了 33 种人类癌症,以研究编码 mG 写入器的基因的异常变化。

结果

我们证明 mG 写入器在人类癌症中失调,并与生存率降低显著相关。通过将患者分为高 mG 评分和低 mG 评分组,我们表明低 mG 评分通常与免疫浸润和对免疫治疗的更好反应相关。

结论

我们的分析表明 mG 写入器在各种癌症中的遗传改变、表达模式和临床相关性。本研究为 mG 写入器表达作为癌症生物标志物的潜在应用提供了见解,并提出了针对 mG 写入器进行癌症治疗的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a95f/11264101/4759b4ca73c7/CNR2-7-e2138-g001.jpg

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