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      Expression pattern and prognostic value of key regulators for N7-methylguanosine RNA modification in prostate cancer : m7G RNA modification in PCa

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          Abstract

          Alterations in the regulators of RNA methylation modifications, such as N7-methylguanosine (m7G), have been implicated in a variety of diseases. Therefore, the analysis and identification of disease-related m7G modification regulators will accelerate advances in understanding disease pathogenesis. However, the implications of alterations in the regulators of m7G modifications remain poorly understood in prostate adenocarcinoma. In the present study, we analyze the expression patterns of 29 m7G RNA modification regulators in prostate adenocarcinoma using The Cancer Genome Atlas (TCGA) and perform consistent clustering analysis of differentially expressed genes (DEGs). We find that 18 m7G-related genes are differentially expressed in tumor and normal tissues. In different cluster subgroups, DEGs are mainly enriched in tumorigenesis and tumor development. Furthermore, immune analyses demonstrate that patients in cluster 1 have significantly higher scores for stromal and immune cells, such as B cells, T cells, and macrophages. Then, a TCGA-related risk model is developed and successfully validated using a Gene Expression Omnibus external dataset. Two genes ( EIF4A1 and NCBP2) are determined to be prognostically significant. Most importantly, we construct tissue microarrays from 26 tumor specimens and 20 normal specimens, and further confirm that EIF4A1 and NCBP2 are associated with tumor progression and Gleason score. Therefore, we conclude that the m7G RNA methylation regulators may be involved in the poor prognosis of patients with prostate adenocarcinoma. The results of this study may provide support for exploring the underlying molecular mechanisms of m7G regulators, especially EIF4A1 and NCBP2.

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          Most cited references45

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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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            Understanding the tumor immune microenvironment (TIME) for effective therapy

            The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
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              The Tumor Microenvironment Innately Modulates Cancer Progression

              Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and NK cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Crosstalk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.
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                Author and article information

                Journal
                Acta Biochim Biophys Sin (Shanghai)
                Acta Biochim Biophys Sin (Shanghai)
                ABBS
                Acta Biochimica et Biophysica Sinica
                Oxford University Press
                1672-9145
                1745-7270
                22 February 2023
                April 2023
                22 February 2023
                : 55
                : 4
                : 561-573
                Affiliations
                [1 ] orgnameDepartment of Urology orgnameNanfang Hospital orgnameSouthern Medical University Guangzhou 510515 China
                [2 ] orgnameDepartment of Urology orgnameGanzhou People’s Hospital Ganzhou 341000 China
                [3 ] orgnameDepartment of Anesthesiology orgnameNanfang Hospital orgnameSouthern Medical University Guangzhou 510515 China
                [4Department ] orgnameof Pathology orgnameGanzhou People′s Hospital Ganzhou 341000 China
                [5 ] orgnameDepartment of Urology orgnameZhuhai People’s Hospital (Zhuhai Hospital affiliated with Jinan University) Zhuhai 519000 China
                Author notes
                [ † ]

                These authors contributed equally to this work.

                Correspondence address. Tel: +86-20-61641765; (Q.W.) / Tel: +86-756-2222569; (G.P.) qwei@smu.edu.cnpangguofu010919@163.com
                Article
                10.3724/abbs.2023017
                10195147
                36810782
                5a393673-7bbd-42ca-920f-806d385cfd5e
                © The Author(s) 2021.

                0

                This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).

                History
                : 1 August 2022
                : 8 October 2022
                Funding
                Funded by: a grant from the National Natural Science Foundation of China
                Award ID: No.
                Award ID: 81502577
                This work was supported by a grant from the National Natural Science Foundation of China (No. 81502577).
                Categories
                Research Article
                Custom metadata
                Q Zhai, Y Hou, Y Ye, S Dai, G Guo, Q Yang, G Pang, et al. Expression pattern and prognostic value of key regulators for N7-methylguanosine RNA modification in prostate cancer. Acta Biochim Biophys Sin, 2023, Vol.: fpage–lpage, https://doi.org/10.3724/abbs.2023017
                2023/2/14 16:34:07
                Q Zhai
                Q Zhai, Y Hou, Y Ye, S Dai, G Guo, Q Yang, G Pang, et al.
                Expression pattern and prognostic value of key regulators for N7-methylguanosine RNA modification in prostate cancer

                prostate cancer,m7g,rna modification,tumor microenvironment,tissue microarray

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