RNAMethyPro : a biologically conserved signature of N6-methyladenosine regulators for predicting survival at pan-cancer level

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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Author(s)

  • Raju Kandimalla
  • Jia Ke
  • Linjie Zhao
  • Shengtao Zhou
  • Ajay Goel

Detail(s)

Original languageEnglish
Article number13
Journal / Publicationnpj Precision Oncology
Volume3
Early online date1 May 2019
Publication statusPublished - 2019

Link(s)

Abstract

Accumulating evidence indicates the role of N6-methyladenosine (m6 A) 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 m6A 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 m6A 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 m6A 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.

Research Area(s)

  • MESSENGER-RNA METHYLATION, STEM-LIKE CELLS, MYELOID-LEUKEMIA, BREAST-CANCER, NUCLEAR-RNA, M(6)A, EXPRESSION, TRANSLATION, DIFFERENTIATION, DEMETHYLASE

Citation Format(s)

RNAMethyPro : a biologically conserved signature of N6-methyladenosine regulators for predicting survival at pan-cancer level. / Kandimalla, Raju; Gao, Feng; Li, Ying; Huang, Hao; Ke, Jia; Deng, Xin; Zhao, Linjie; Zhou, Shengtao; Goel, Ajay; Wang, Xin.

In: npj Precision Oncology, Vol. 3, 13, 2019.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review