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      Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway

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          Abstract

          Background

          Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression.

          Methods

          GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database. Subsequent verification of GNL3L protein expression in ESCC, coupled with clinical data, was conducted through immunohistochemistry and followed by a comprehensive prognostic analysis. We further investigated potential signaling pathways facilitating ESCC progression, employing a combination of bioinformatics analysis and immunohistochemical (IHC) experiments.

          Results

          Bioinformatics analysis unveiled a significant elevation in GNL3L expression, particularly in gastrointestinal tumors and ESCC. Immunohistochemistry confirmed elevated GNL3L expression in ESCC tissues. Regression analysis established a correlation between elevated GNL3L expression and advanced tumor node metastasis (TNM) stage, with high expression associated with poor prognosis in patients with ESCC. Our integrated approach of bioinformatics and IHC analysis indicated a potential role of the signal transducers and activators of transcription 3 (STAT3) signaling pathway in ESCC progression.

          Conclusions

          High GNL3L expression significantly contributes to the malignant progression of ESCC. This study further elucidates the mechanisms driving ESCC progression and offers possible insights for more effective diagnosis and treatment strategies.

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          Most cited references25

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

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            KEGG: kyoto encyclopedia of genes and genomes.

            M Kanehisa (2000)
            KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).
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              GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses

              Zefang Tang, Chenwei Li, Boxi Kang … (2017)
              Abstract Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.
              Article 0 comments Cited 3782 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Thorac Dis
                Journal ID (iso-abbrev): J Thorac Dis
                Journal ID (publisher-id): JTD
                Title: Journal of Thoracic Disease
                Publisher: AME Publishing Company
                ISSN (Print): 2072-1439
                ISSN (Electronic): 2077-6624
                Publication date (Electronic): 29 April 2024
                Publication date (Print): 30 April 2024
                Volume: 16
                Issue: 4
                Pages: 2580-2590
                Affiliations
                [1 ]deptDepartment of Thoracic Surgery , Fujian Medical University Union Hospital , Fuzhou, China;
                [2 ]deptDepartment of Pathology , Pingtan Branch of Fujian Medical University Union Hospital , Fuzhou, China;
                [3 ]deptDepartment of Internal Medicine , Medstar Southern Maryland Hospital Center , Clinton, MD, USA;
                [4 ]The Australian Paediatric Surveillance Unit (APSU), The University of Sydney , deptThe Children's Hospital , Westmead, New South Wales, Australia;
                [5 ]deptChao Family Comprehensive Cancer Center , University of California Irvine , Orange, CA, USA;
                [6 ]deptKey Laboratory of Cardio-Thoracic Surgery , Fujian Medical University , Fuzhou, China;
                [7 ]deptKey Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Science , Fujian Medical University , Fuzhou, China;
                [8 ]deptFujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology , Fujian Medical University , Fuzhou, China
                Author notes

                Contributions: (I) Conception and design: S Chen, S Yu; (II) Administrative support: S Chen, Z Xiang; (III) Provision of study materials or patients: P Zhang; (IV) Collection and assembly of data: S Xu; (V) Data analysis and interpretation: S Xu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Shuchen Chen, MD, PhD. Department of Thoracic Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China; Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer, Ministry of Education, School of Basic Medical Science, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China. Email: cscdoctor@ 123456163.com ; Zhang Xiang, MD. Department of Pathology, Pingtan Branch of Fujian Medical University Union Hospital, Linhu 7 th Road, Fuzhou 350001, China. Email: 752594766@ 123456qq.com .
                Article
                Publisher ID: jtd-16-04-2580
                DOI: 10.21037/jtd-24-473
                PMC ID: 11087641
                PubMed ID: 38738247
                SO-VID: 320414b3-2267-4626-bfec-613f9b134a7e
                Copyright © 2024 Journal of Thoracic Disease. All rights reserved.
                License:

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                Date received : 21 March 2024
                Date accepted : 19 April 2024
                Funding
                Funded by: the Joint Funds for the Innovation of Science and Technology, Fujian Province
                Award ID: Nos. 2020Y9076 and 2020Y92010195
                Funded by: the National Natural Science Foundation of China
                Award ID: No. 82273415
                Funded by: the Natural Science Foundation of Fujian Province
                Award ID: Nos. 2020J011004 and 2023J01122892
                Funded by: the Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University; the Fujian Provincial Health Technology Project
                Award ID: No. 2020CXA028
                Funded by: the Cohort Study of the School of Public Health, Fujian Medical University
                Award ID: No. 2021HX003
                Categories
                Subject: Original Article

                Keywords: guanine nucleotide-binding protein like 3-like (gnl3l),esophageal squamous cell carcinoma (escc),clinical significance,malignant progression,signal transducers and activators of transcription 3 (stat3)
                Data availability:
                Keywords: guanine nucleotide-binding protein like 3-like (gnl3l), esophageal squamous cell carcinoma (escc), clinical significance, malignant progression, signal transducers and activators of transcription 3 (stat3)

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