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      Gene Characteristics and Prognostic Values of m 6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

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          Abstract

          Background

          N 6-methyladenosine (m 6A) is the most common internal modification present in mRNAs and long noncoding RNAs (lncRNAs), associated with tumorigenesis and cancer progression. However, little is known about the roles of m 6A and its regulatory genes in nonsmall cell lung cancer (NSCLC). Here, we systematically explored the roles and prognostic significance of m 6A-associated regulatory genes in NSCLC.

          Methods

          The copy number variation (CNV), mutation, mRNA expression data, and corresponding clinical pathology information of 1057 NSCLC patients were downloaded from the cancer genome atlas (TCGA) database. The gain and loss levels of CNVs were determined by utilizing segmentation analysis and GISTIC algorithm. The GSEA was conducted to explore the functions related to different levels of m 6A regulatory genes. Logrank test was utilized to assess the prognostic significance of m 6A-related gene's CNV.

          Results

          The genetic alterations of ten m 6A-associated regulators were identified in 102 independent NSCLC samples and significantly related to advanced tumor stage. Deletions or shallow deletions corresponded to lower mRNA expression while copy number gains or amplifications were related to increased mRNA expression of m 6A regulatory genes. Survival analysis showed the patients with copy number loss of FTO with worse disease-free survival (DFS) or overall survival (OS). Besides, copy number loss of YTHDC2 was also with poor OS for NSCLC patients. Moreover, high FTO expression was significantly associated with oxidative phosphorylation, translation, and metabolism of mRNA.

          Conclusion

          Our findings provide novel insight for better understanding of the roles of m 6A regulators and RNA epigenetic modification in the pathogenesis of NSCLC.

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          Most cited references 53

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

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            Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

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              Cancer Statistics, 2021

              Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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                Author and article information

                Contributors
                Journal
                J Healthc Eng
                J Healthc Eng
                JHE
                Journal of Healthcare Engineering
                Hindawi
                2040-2295
                2040-2309
                2021
                29 July 2021
                : 2021
                Affiliations
                1Department of Pathology, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
                2Department of Clinical Laboratory, Maternal and Child Care Hospital, Changsha, Hunan, China
                3Department of Geriatrics, Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, China
                Author notes

                Academic Editor: Dr. Dilbag Singh

                Article
                10.1155/2021/2257066
                8346307
                34367534
                Copyright © 2021 Na Li et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2019JJ50425
                Award ID: 2020JJ5909
                Funded by: Education Department of Hunan Province
                Award ID: 18C1129
                Categories
                Research Article

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