Prognostic Value of Genomic Instability of m <sup>6</sup>A-Related lncRNAs in Lung Adenocarcinoma

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background: Genomic instability of N6-methyladenosine (m ⁶A)–related long noncoding RNAs (lncRNAs) plays a pivotal role in the tumorigenesis of lung adenocarcinoma (LUAD). Our study identified a signature of genomic instability of m ⁶A-associated lncRNA signature and revealed its prognostic role in LUAD.

Methods: We downloaded RNA-sequencing data and somatic mutation data for LUAD from The Cancer Genome Atlas (TCGA) and the GSE102287 dataset from the Gene Expression Omnibus (GEO) database. The “Limma” R package was used to identify a network of regulatory m ⁶A-related lncRNAs. We used the Wilcoxon test method to identify genomic-instability–derived m ⁶A-related lncRNAs. A competing endogenous RNA (ceRNA) network was constructed to identify the mechanism of the genomic instability of m ⁶A-related lncRNAs. Univariate and multivariate Cox regression analyses were performed to construct a prognostic model for internal testing and validation of the prognostic m ⁶A-related lncRNAs using the GEO dataset. Performance analysis was conducted to compare our prognostic model with the previously published lncRNA models. The CIBERSORT algorithm was used to explore the relationship of m ⁶A-related lncRNAs and the immune microenvironment. Prognostic m ⁶A-related lncRNAs in prognosis, the tumor microenvironment, stemness scores, and anticancer drug sensitivity were analyzed to explore the role of prognostic m ⁶A-related lncRNAs in LUAD.

Results: A total of 42 genomic instability–derived m ⁶A-related lncRNAs were differentially expressed between the GS (genomic stable) and GU (genomic unstable) groups of LUAD patients. Four differentially expressed lncRNAs, 17 differentially expressed microRNAs, and 75 differentially expressed mRNAs were involved in the genomic-instability–derived m ⁶A-related lncRNA-mediated ceRNA network. A prediction model based on 17 prognostic m ⁶A-associated lncRNAs was constructed based on three TCGA datasets (all, training, and testing) and validated in the GSE102287 dataset. Performance comparison analysis showed that our prediction model (area under the curve [AUC] = 0.746) could better predict the survival of LUAD patients than the previously published lncRNA models (AUC = 0.577, AUC = 0.681). Prognostic m ⁶A-related-lncRNAs have pivotal roles in the tumor microenvironment, stemness scores, and anticancer drug sensitivity of LUAD.

Conclusion: A signature of genomic instability of m ⁶A-associated lncRNAs to predict the survival of LUAD patients was validated. The prognostic, immune microenvironment and anticancer drug sensitivity analysis shed new light on the potential novel therapeutic targets in LUAD.

Related collections

Most cited references 42

Record: found
Abstract: found
Article: not found

Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)

This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.

0 comments Cited 27141 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Global cancer statistics, 2012.

Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)

Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.

0 comments Cited 3834 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genomic instability--an evolving hallmark of cancer.

Simona Negrini, Vassilis G. Gorgoulis, Thanos Halazonetis (2010)

Genomic instability is a characteristic of most cancers. In hereditary cancers, genomic instability results from mutations in DNA repair genes and drives cancer development, as predicted by the mutator hypothesis. In sporadic (non-hereditary) cancers the molecular basis of genomic instability remains unclear, but recent high-throughput sequencing studies suggest that mutations in DNA repair genes are infrequent before therapy, arguing against the mutator hypothesis for these cancers. Instead, the mutation patterns of the tumour suppressor TP53 (which encodes p53), ataxia telangiectasia mutated (ATM) and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF) support the oncogene-induced DNA replication stress model, which attributes genomic instability and TP53 and ATM mutations to oncogene-induced DNA damage.

0 comments Cited 385 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Rui Li: URI : https://loop.frontiersin.org/people/1063618/overview

Jian-Ping Li: URI : https://loop.frontiersin.org/people/1062338/overview

Ting-Ting Liu: URI : https://loop.frontiersin.org/people/1101001/overview

Chen Huo: URI : https://loop.frontiersin.org/people/1101236/overview

Jie Yao: URI : https://loop.frontiersin.org/people/1100963/overview

Xiu-Li Ji: URI : https://loop.frontiersin.org/people/1351833/overview

Yi-Qing Qu: URI : https://loop.frontiersin.org/people/734539/overview

Journal

Journal ID (nlm-ta): Front Cell Dev Biol

Journal ID (iso-abbrev): Front Cell Dev Biol

Journal ID (publisher-id): Front. Cell Dev. Biol.

Title: Frontiers in Cell and Developmental Biology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-634X

Publication date (Electronic): 03 March 2022

Publication date Collection: 2022

Volume: 10

Electronic Location Identifier: 707405

Affiliations

[1] ¹ Shandong Key Laboratory of Infectious Respiratory Diseases , Department of Pulmonary and Critical Care Medicine , Qilu Hospital , Cheeloo College of Medicine , Shandong University , Jinan, China

[2] ² Department of Pulmonary Disease , Traditional Chinese Medicine Hospital of Jinan , Jinan, China

[3] ³ Shandong Key Laboratory of Infectious Respiratory Diseases , Department of Pulmonary and Critical Care Medicine , Qilu Hospital of Shandong University , Jinan, China

Author notes

Edited by: Zexian Liu, Sun Yat-sen University Cancer Center (SYSUCC), China

Reviewed by: Yuting He, First Affiliated Hospital of Zhengzhou University, China

Agnese Po, Sapienza University of Rome, Italy

Jingwu Xie, Indiana University, United States

*Correspondence: Yi-Qing Qu, quyiqing@ 123456sdu.edu.cn

This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Cell and Developmental Biology

Article

Publisher ID: 707405

DOI: 10.3389/fcell.2022.707405

PMC ID: 8928224

PubMed ID: 35309906

SO-VID: f7996bae-8056-4107-912c-1e56d0eabce3

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) 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.

History

Date received : 10 May 2021

Date accepted : 09 February 2022

Comments

Comment on this article

scite_

Cited by 2

See all cited by

Most referenced authors 828

See all reference authors

- Version 1