RNAMethyPro: a Biologically Conserved Signature of N6-methyladenosine Regulators for Predicting Survival at Pan-cancer Level

Overview

Journal NPJ Precis Oncol

Publisher Springer Nature

Specialty Oncology

Date 2019 May 10

PMID 31069256

Citations 15

Authors

Raju Kandimalla

Feng Gao

Ying Li

Hao Huang

Jia Ke

Xin Deng

Linjie Zhao

Shengtao Zhou

Ajay Goel

Xin Wang

Affiliations

Soon will be listed here.

Abstract

Accumulating evidence indicates the role of -methyladenosine (mA) regulator-mediated RNA methylation in cancer progression and metastasis; yet its potential clinical significance, if any, remains unclear. In this first-of-its-kind study, we systematically evaluated the role of mA regulators as potential disease biomarkers based on comprehensive analysis of gene expression profiles of 9770 cancer cell lines and clinical specimens from 25 publicly available datasets, encompassing 13 human cancers. We developed and established RNAMethyPro-a gene expression signature of seven mA regulators, which robustly predicted patient survival in multiple human cancers. Pan-cancer analysis identified activated epithelial-mesenchymal transition (EMT), as a highly conserved pathway in high-risk patients predicted by RNAMethyPro in 10 of the 13 cancer types. A network-based analysis revealed an intimate functional interplay between mA regulators and EMT-associated factors via druggable targets such as XPO1 and NTRK1. Finally, the clinical significance of RNAMethyPro was further exemplified in colorectal cancer, where high-risk patients demonstrated strong associations with a mesenchymal subtype, activated stromal infiltration, and poor therapeutic response to targeted anti-EGFR therapy. In summary, RNAMethyPro is a novel, EMT-associated prognostic gene-expression signature in multiple human cancers and may offer an important clinical decision-making tool in the future.

Citing Articles

N6-methyladenosine (m6A) as a regulator of carcinogenesis and drug resistance by targeting epithelial-mesenchymal transition and cancer stem cells.

Wang C, Ma D, Yu H, Zhuo Z, Ye Z Heliyon. 2023; 9(3):e14001.

PMID: 36915498 PMC: 10006539. DOI: 10.1016/j.heliyon.2023.e14001.

Targeting FTO Suppresses Pancreatic Carcinogenesis via Regulating Stem Cell Maintenance and EMT Pathway.

Garg R, Melstrom L, Chen J, He C, Goel A Cancers (Basel). 2022; 14(23).

PMID: 36497402 PMC: 9737034. DOI: 10.3390/cancers14235919.

The emerging therapeutic target of dynamic and reversible N6-methyladenosine modification during cancer development.

Liu S, Chen S, Tang C, Zhao Y, Cui W, Jia L Front Oncol. 2022; 12:970833.

PMID: 36226062 PMC: 9548694. DOI: 10.3389/fonc.2022.970833.

Pan-sarcoma characterization of lncRNAs in the crosstalk of EMT and tumour immunity identifies distinct clinical outcomes and potential implications for immunotherapy.

Shi D, Mu S, Pu F, Zhong B, Hu B, Muhtar M Cell Mol Life Sci. 2022; 79(8):427.

PMID: 35842562 PMC: 11071722. DOI: 10.1007/s00018-022-04462-4.

Emerging Roles of mA RNA Methylation Regulators in Gynecological Cancer.

Huang W, Kong F, Li R, Chen X, Wang K Front Oncol. 2022; 12:827956.

PMID: 35155260 PMC: 8831694. DOI: 10.3389/fonc.2022.827956.

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