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      TCN1 is a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma

      research-article
      , ,
      World Journal of Surgical Oncology
      BioMed Central
      TCN1, LUAD, Prognosis, Immune infiltrates

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          Abstract

          Background

          Around the world, lung cancer is the leading cause of cancer-related death. Lung adenocarcinomas are among the most common diagnosed forms of lung cancer, whose overall survival has not improved significantly, which makes finding an effective therapeutic target vital. Transcobalamin (TCN1) is a vitamin B12-binding protein which regulates cobalamin homeostasis. In tumor tissues, TCN1 is expressed highly, and its expression is correlated with cancer aggressiveness and poor prognosis according to recent studies and bioinformatic analyses. However, its effect on lung adenocarcinoma (LUAD) is unknown.

          Methods

          We evaluated whether TCN1 shows diagnostic and prognostic value in LUAD using bioinformatic analysis. In particular, various databases and analysis tools were used to determine TCN1’s relationship with LUAD, including TCGA, GTEx, GEO, STRING, and TISIDB.

          Results

          As compared to normal lung tissue, the level of TCN1 expression in LUAD tissues was significantly higher ( P < 0.001). TCN1 also had a good ability to distinguish lung adenocarcinoma from non-lung adenocarcinoma samples [area under the curve (AUC) = 0.788]. According to univariate Cox statistics, high expression levels of TCN1 correlate with poor overall survival (OS) in LUAD ( P < 0.001). Moreover, based on a multivariate Cox analysis, TCN1 expression was independently correlated with OS ( P = 0.011). GO/KEGG and GSEA indicated enrichment in epidermal cell differentiation ( P < 0.0005), keratinocyte differentiation ( P < 0.0005), neuroactive ligand–receptor interaction ( P < 0.0005), epithelial–mesenchymal transition ( P = 0.029, FDR = 0.023) and TNFA signaling via NFKB ( P = 0.029, FDR = 0.023). Furthermore, TCN1 is associated with immune infiltration based on an analysis of immune cell infiltration.

          Conclusions

          In summary, TCN1 could be used as a prognostic and diagnostic biomarker and provide deeper perspectives for the development of therapies and prognostic markers in LUAD.

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          Most cited references33

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          STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets

          Abstract Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein–protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein–protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
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            Lung cancer: current therapies and new targeted treatments.

            Lung cancer is the most frequent cause of cancer-related deaths worldwide. Every year, 1·8 million people are diagnosed with lung cancer, and 1·6 million people die as a result of the disease. 5-year survival rates vary from 4-17% depending on stage and regional differences. In this Seminar, we discuss existing treatment for patients with lung cancer and the promise of precision medicine, with special emphasis on new targeted therapies. Some subgroups, eg-patients with poor performance status and elderly patients-are not specifically addressed, because these groups require special treatment considerations and no frameworks have been established in terms of new targeted therapies. We discuss prevention and early detection of lung cancer with an emphasis on lung cancer screening. Although we acknowledge the importance of smoking prevention and cessation, this is a large topic beyond the scope of this Seminar.
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              Immune checkpoint blockade: a common denominator approach to cancer therapy.

              The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study. Copyright © 2015 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                zhigang_cai@163.com
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                14 March 2022
                14 March 2022
                2022
                : 20
                : 83
                Affiliations
                GRID grid.452702.6, ISNI 0000 0004 1804 3009, Department of Respiratory and Critical Care Medicine, , The Second Hospital of Hebei Medical University, ; No.215 Heping West Road, Shijiazhuang, Hebei Province China
                Article
                2556
                10.1186/s12957-022-02556-8
                8922850
                35287670
                f8d660ee-cf91-4cc4-8751-660ed487a370
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 18 November 2021
                : 3 March 2022
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Surgery
                tcn1,luad,prognosis,immune infiltrates
                Surgery
                tcn1, luad, prognosis, immune infiltrates

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