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      Recent advances in gastric cancer early diagnosis

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          Abstract

          Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

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          Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

          The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
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            Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer.

            Long intergenic non-protein-coding RNA 152 (LINC00152) is one of the long noncoding RNAs (lncRNAs) abnormally expressed in gastric cancer tissues. However, its value in the diagnosis of gastric cancer is unclear. The aim of this study is to evaluate the clinical significance of plasma LINC00152 as a biomarker in the screening of gastric cancer and to explore the possible mechanism underling its stable existence in blood. We analyzed the levels of plasma LINC00152 in patients with gastric cancer and gastric epithelial dysplasia and healthy controls using quantitative reverse transcription polymerase chain reaction and then confirmed by sequencing. We also compared its levels in paired preoperative and postoperative plasma samples. In addition, we compared the levels of LINC00152 in plasma and in exosomes, which were extracted from the same plasma and confirmed by transmission electron microscopy. The levels of plasma LINC00152 were significantly elevated in gastric cancer patients compared with healthy controls. The sensitivity and specificity of plasma LINC00152 in the diagnosis of gastric cancer were 48.1 and 85.2%, respectively. There were no significant differences of LINC00152 levels between gastric epithelial dysplasia patients and healthy controls. LINC00152 levels in preoperative plasma samples were lower than those in postoperative ones. There were also no differences between LINC00152 levels in plasma and in exosomes. All these results suggested that LINC00152 can be detected in plasma, and one of the possible mechanisms of its stable existence in blood was protected by exosomes. It has the possibility to be applied in gastric cancer diagnosis as a novel blood-based biomarker.
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              Biomarkers of gastric cancer: Current topics and future perspective

              Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                7 May 2019
                7 May 2019
                : 25
                : 17
                : 2029-2044
                Affiliations
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Faculty of Medicine, Titu Maiorescu University, Bucharest 040441, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
                Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania. mihaela.chivu@ 123456gmail.com
                Author notes

                Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.

                Supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, No. PN-III-P4-ID-PCCF2016-0158 (contract PCCF 17/2018), within PNCDI III.

                Corresponding author: Mihaela Chivu-Economescu, PhD, Research Assistant Professor, Research Scientist, Senior Researcher, Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 285 Mihai Bravu Ave, Bucharest 030304, Romania. mihaela.chivu@ 123456gmail.com

                Telephone: +40-21-3242590 Fax: +40-21-3242590

                Article
                jWJG.v25.i17.pg2029
                10.3748/wjg.v25.i17.2029
                6506585
                31114131
                740e5843-d580-46b0-9618-03273d2e1822
                ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 19 March 2019
                : 3 April 2019
                : 19 April 2019
                Categories
                Review

                biomarkers,gastric cancer,early diagnosis,genetic and epigenetic alterations,circulating molecules

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