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      The Indication of Poor Prognosis by High Expression of ENO1 in Squamous Cell Carcinoma of the Lung

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          Abstract

          The purpose of this study is to investigate the significance of alpha-enolase (ENO1) expression in squamous cell carcinoma of the lung (LUSC), its prognostic value, and prospective molecular mechanism. Using multiplatforms data, including in-house immunohistochemistry, in-house real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), in-house microarray, and public high-throughput data, the expression significance and prognostic role of ENO1 in LUSC tissues were analyzed comprehensively. With the combination of all eligible cases, compared with 941 non-LUSC lung tissues, ENO1 was significantly overexpressed in 1163 cases of LUSC (standardized mean difference (SMD) = 1.23, 95% confidence interval (CI) = 0.76–1.70, P < 0.001). ENO1 also displayed a great ability to differentiate LUSC tissues from non-LUSC lung tissues (AUC = 0.8705) with the comprehensive sensitivity being 0.88 [0.83–0.92], and comprehensive specificity being 0.89 [0.84–0.94]). Moreover, in 1860 cases of LUSC with survival information, patients with higher expression of ENO1 had poorer prognosis (hazard ratio (HR) = 1.20, 95% CI = 1.01–1.43, P = 0.043). ENO1 and its related genes mainly participated in the pathways of cell division and proliferation. In conclusion, the upregulation of ENO1 could affect the carcinogenesis and unfavorable outcome of LUSC.

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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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            RNA sequencing: the teenage years

            Over the past decade, RNA sequencing (RNA-seq) has become an indispensable tool for transcriptome-wide analysis of differential gene expression and differential splicing of mRNAs. However, as next-generation sequencing technologies have developed, so too has RNA-seq. Now, RNA-seq methods are available for studying many different aspects of RNA biology, including single-cell gene expression, translation (the translatome) and RNA structure (the structurome). Exciting new applications are being explored, such as spatial transcriptomics (spatialomics). Together with new long-read and direct RNA-seq technologies and better computational tools for data analysis, innovations in RNA-seq are contributing to a fuller understanding of RNA biology, from questions such as when and where transcription occurs to the folding and intermolecular interactions that govern RNA function.
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              c ircTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1

              Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the role of circRNA in lung squamous cell carcinoma (LUSC) remains largely unknown. Herein, we explore the expression profiles of circRNA and mRNA in 5 paired samples of LUSC. By analyzing the co-expression network of differentially expressed circRNAs and dysregulated mRNAs, we identify that a cell cycle-related circRNA, circTP63, is upregulated in LUSC tissues and its upregulation is correlated with larger tumor size and higher TNM stage in LUSC patients. Elevated circTP63 promotes cell proliferation both in vitro and in vivo. Mechanistically, circTP63 shares miRNA response elements with FOXM1. circTP63 competitively binds to miR-873-3p and prevents miR-873-3p to decrease the level of FOXM1, which upregulates CENPA and CENPB, and finally facilitates cell cycle progression.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                jo
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2021
                30 August 2021
                : 2021
                : 9910962
                Affiliations
                1Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, China
                2Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, China
                3Ward of Pulmonary and Critical Care Medicine, Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, China
                4Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
                5Department of Cardio-Thoracic Surgery, The Seventh Affiliated Hospital of Guangxi Medical University, Wuzhou Gongren Hospital, Wuzhou, No. 1, Gaodi Road, Guangxi Zhuang Autonomous Region 543000, China
                Author notes

                Academic Editor: Xiangya Ding

                Author information
                https://orcid.org/0000-0003-0461-7182
                https://orcid.org/0000-0003-2402-2987
                https://orcid.org/0000-0003-4132-2973
                https://orcid.org/0000-0002-7793-1239
                https://orcid.org/0000-0002-5147-085X
                https://orcid.org/0000-0002-2267-3164
                https://orcid.org/0000-0003-4065-7886
                https://orcid.org/0000-0001-8714-2906
                https://orcid.org/0000-0003-2024-2317
                https://orcid.org/0000-0003-3852-3459
                https://orcid.org/0000-0002-6485-1336
                Article
                10.1155/2021/9910962
                8423576
                34504528
                00263c36-bd21-431e-8290-53463333a832
                Copyright © 2021 Wan-Ying Huang 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.

                History
                : 21 March 2021
                : 27 June 2021
                : 19 August 2021
                Funding
                Funded by: Guangxi Zhuang Autonomous Region Health and Family Planning Commission
                Award ID: Z20180483
                Funded by: Guangxi Degree and Postgraduate Education Reform and Development Research Projects
                Award ID: JGY2019050
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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