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      Metabolomics study identified bile acids as potential biomarkers for gastric cancer: A case control study

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          Abstract

          Gastric cancer (GC) is a common lethal malignancy worldwide. Gastroscopy is an effective screening technique for decreasing mortality. However, there are still limited useful non-invasive markers for early detection of GC. Bile acids are important molecules for the modulation of energy metabolism. With an in-depth targeted method for accurate quantitation of 80 bile acids (BAs), we aimed to find potential biomarkers for the early screening of GC. A cohort with 280 participants was enrolled, including 113 GC, 22 benign gastric lesions (BGL) and 145 healthy controls. Potential markers were identified using a random forest machine algorithm in the discovery cohort (n=180), then validated in an internal validation cohort (n=78) and a group with 22 BGL. The results represented significant alterations in the circulating BA pool between GC and the controls. BAs also exhibited significant correlations with various clinical traits. Then, we developed a diagnostic panel that comprised six BAs or ratios for GC detection. The panel showed high accuracy for the diagnosis of GC with AUC of 1 (95%CI: 1.00-1.00) and 0.98 (95%CI: 0.93-1.00) in the discovery and validation cohort, respectively. This 6-BAs panel was also able to identify early GC with AUC of 1 (95%CI: 0.999-1.00) and 0.94 (95%CI: 0.83-1.00) in the discovery and validation cohort, respectively. Meanwhile, this panel achieved a good differential diagnosis between GC and BGL and the AUC was 0.873 (95%CI: 0.812-0.934). The alternations of serum bile acids are characteristic metabolic features of GC. Bile acids could be promising biomarkers for the early diagnosis of GC.

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          Most cited references47

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Cytoscape: a software environment for integrated models of biomolecular interaction networks.

            Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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              Cancer statistics, 2019

              Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, 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, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                18 November 2022
                2022
                : 13
                : 1039786
                Affiliations
                [1] 1 Department of General Surgery, First Affiliated Hospital of Dalian Medical University , Dalian, China
                [2] 2 Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University , Dalian, China
                [3] 3 Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, China
                [4] 4 Department of Hepato-Biliary-Pancreas, Affiliated Hospital of North Sichuan Medical College , Nanchong, China
                [5] 5 iPhenome Biotechnology (Yun Pu Kang) Inc. , Dalian, China
                [6] 6 Institute of Integrative Medicine, Dalian Medical University , Dalian, China
                Author notes

                Edited by: Bertrand Duvillie, Institut Curie, France

                Reviewed by: Guozhu Ye, Institute of Urban Environment (CAS), China; Jarlei Fiamoncini, University of São Paulo, Brazil

                *Correspondence: Yanfeng Liu, u202918@ 123456163.com ; Peiyuan Yin, yinpeiyuan@ 123456dmu.edu.cn

                †These authors have contributed equally to this work

                This article was submitted to Cancer Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.1039786
                9715751
                36465663
                58c177b8-f5ad-40fa-bffb-5abf86fab11f
                Copyright © 2022 Pan, Deng, Wei, Wu, Zhang, Yuan, Liang, Liu and Yin

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 September 2022
                : 03 November 2022
                Page count
                Figures: 7, Tables: 2, Equations: 0, References: 47, Pages: 14, Words: 4971
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                gastric cancer,bile acids,metabolomics,biomarkers,lc ms
                Endocrinology & Diabetes
                gastric cancer, bile acids, metabolomics, biomarkers, lc ms

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