Open Access Journal Article

Comprehensive analyses reveal molecular and clinical characteristics of RNA modification writers across 32 cancer types

by Jiayu Ding a,b,c,1 ,  Hao Shen a,b,c,1 ,  Jiaying Ji a,b,c,1 ,  Jiaxing Li a,b,c ,  Wenbin Kuang a,b,c ,  Zhongrui Shi a,b,c ,  Dawei Wang a,b,c ,  Yuanyuan Chen a,b,c ,  Didi Wan d,* ,  Xiao Wang a,b,c,*  and  Peng Yang a,b,c,* orcid
a
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
b
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
c
Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China
d
BGI College & Henan Institute of Medical and Pharmaceutical Sciences Zhengzhou University, Zhengzhou 450052, China
*
Author to whom correspondence should be addressed.
CI  2024 3(2):36; https://doi.org/10.58567/ci03020004
Received: 27 December 2023 / Accepted: 24 January 2024 / Published Online: 25 January 2024
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Abstract

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.

Keywords: RNA modification writer; pan-cancer; genomics; prognosis; tumor immune microenvironment;
Copyright: © 2024 by Ding, Shen, Ji, Li, Kuang, Shi, Wang, Chen, Wan, Wang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funding

National Key R&D Program of China (2022YFA1303803) , National Natural Science Foundation of China (82073701) , Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (SKLNMZZ202209) , Natural Science Foundation of Jiangsu Province (BK20231013)

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ACS Style
Ding, J.; Shen, H.; Ji, J.; Li, J.; Kuang, W.; Shi, Z.; Wang, D.; Chen, Y.; Wan, D.; Wang, X.; Yang, P. Comprehensive analyses reveal molecular and clinical characteristics of RNA modification writers across 32 cancer types. Cancer Insight, 2024, 3, 36. https://doi.org/10.58567/ci03020004
AMA Style
Ding J, Shen H, Ji J, Li J, Kuang W, Shi Z, Wang D, Chen Y, Wan D, Wang X, Yang P. Comprehensive analyses reveal molecular and clinical characteristics of RNA modification writers across 32 cancer types. Cancer Insight; 2024, 3(2):36. https://doi.org/10.58567/ci03020004
Chicago/Turabian Style
Ding, Jiayu; Shen, Hao; Ji, Jiaying; Li, Jiaxing; Kuang, Wenbin; Shi, Zhongrui; Wang, Dawei; Chen, Yuanyuan; Wan, Didi; Wang, Xiao, and et al. 2024. "Comprehensive analyses reveal molecular and clinical characteristics of RNA modification writers across 32 cancer types" Cancer Insight 3, no.2:36. https://doi.org/10.58567/ci03020004
APA style
Ding, J., Shen, H., Ji, J., Li, J., Kuang, W., Shi, Z., Wang, D., Chen, Y., Wan, D., Wang, X., & Yang, P. (2024). Comprehensive analyses reveal molecular and clinical characteristics of RNA modification writers across 32 cancer types. Cancer Insight, 3(2), 36. https://doi.org/10.58567/ci03020004

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