Pan-Cancer Analysis Links Altered RNA m7G Methyltransferase Expression to Oncogenic Pathways - Immune Cell Infiltrations and Overall Survival

Sep 21, 2026

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N7-methylguanosine (m7G) modification is a common RNA mark in humans, and aberrant m7G writer expression is linked to cancer progression and poorer survival. However, systematic assessments of how frequently m7G writers are dysregulated and how this relates to clinical outcomes across a pan-cancer cohort remain limited. This study analyzes genome, transcriptome, and clinical data across 33 cancers, evaluates molecular alterations in m7G writers, and connects m7G scores with immune infiltration and immunotherapy response.

LanguageEnglish

CategoryResearch & Report

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Pages8

Reading Time20 min

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Abstract

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Description of 33 Types of Cancer From TCGA

Cancer Reports Pan-Cancer Analysis Links Altered RNA m7G Methyltransferase Expression to Oncogenic Pathways, Immune Cell Infiltrations and Overall Survival Anni Su1,2 | Renhua Song1,2 | Justin J.-L. Wong1,2 1Epigenetics and RNA Biology Laboratory, Charles Perkins Centre, University of Sydney, Camperdown, Australia | 2Faculty of Medicine and Health, University of Sydney, Camperdown, Australia Correspondence: Justin J.-L. Wong ([justin.wong@sydney.edu.au](justin.wong@sydney.edu.au)) Received: 18 March 2024 | Revised: 23 June 2024 | Accepted: 30 June 2024 Funding: Justin J.-L. Wong is funded by the National Health and Medical Research Council (Grant \# 2010647), the NSW Health (Grant \# 46014) and the Australian Research Council (Grant \# DP230102041) . ABSTRACT Background: N7-methylguanosine (m7G) modification is one of the most prevalent RNA modifications in humans. Dysregulated m7G modifications caused by aberrant expression of m7G 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 m7G 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 m7G methyltransferase inhuman 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 m7G writers. Result: We demonstrate that m7G writers are dysregulated in human cancers and are associated predominantly with poorer survival. By dividing patients into those with high and low m7G scores, we show that a lower m7G 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 m7G writers across various cancers. This study provides insights into the potential utility of m7G writer expression as a cancer biomarker and proposes the possibility of targeting m7G writers for cancer therapy. 1 | Introduction N7-methylguanosine (m7G) modification is one of the most prevalent RNA modifications in humans that regulates RNA metabolism [1] . m7G is deposited at 5′ cap and internal sites of messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA) and microRNA (miRNA) [1, 2] . So far, the understanding of m7G regulators remains preliminary. Several m7G writers have been identified. Methyltransferase like 1 (METTL1)/WD repeat domain 4 (WDR4) instals m7G on internal mRNA, tRNA and miRNA [3, 4]. The RNA guanine-7 methyltransferase (RNMT)/family with sequence similarity 103 member A1 (FAM103A1) complex regulates the 5′ cap m7G modification [5] . Williams–Beuren syndrome chromosome region 22 protein (WBSCR22)/multifunctional methyltransferase subunit TRM112-like protein (TRMT112) mediates rRNA m7G methylation [6] . However, the lack of reported m7G erasers and readers underscores a significant gap in the current knowledge [2, 7, 8] . Recently, the first internal m7G reader protein, quaking, has been identified [9] . This protein This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC. Cancer Reports, 2024; 7:e2138 1 of 8 [https://doi.org/10.1002/cnr2.2138](https://doi.org/10.1002/cnr2.2138) has been shown to regulate the stability and translational efficiency of a subset of internal m7G-modified transcripts under stress conditions [9] . Although the understanding of m7G regulators is not sufficient, more and more evidence suggests that dysregulated m7G modification mediated by aberrant expression of m7G writers contributes to cancer

FAQs

Why focus on m7G RNA modification and m7G writers in cancer?

m7G is a prevalent RNA modification, and dysregulated m7G writer expression can drive cancer progression and reduce patient survival. Yet, comprehensive pan-cancer evaluations of these writers and their clinical relevance were insufficient.

What data and cancers were analyzed to study m7G writers?

The study used genome, transcriptome, and clinical data from TCGA across 33 human cancer types. It assessed aberrant changes in genes encoding m7G writers.

How do m7G scores relate to immune infiltration and immunotherapy response?

Patients divided into high and low m7G scores showed that a lower m7G score is generally associated with immune infiltration and better response to immunotherapy. Overall, m7G writer dysregulation corresponded predominantly to poorer survival.

Sep 21, 2026

Uploaded by Noah