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      Prognostic value of differentiation status in gastric cancer

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          Abstract

          Background

          Up to date, investigation of the prognostic value of differentiation status mainly focused on signet ring cell and mucinous gastric cancer. Thus, the present study aims to investigate the clinicopathological features and prognosis of gastric cancer patients with well, moderately and poorly differentiation status.

          Methods

          From September 2008 to March 2015, a total of 3090 gastric cancer patients treated with radical D2 gastrectomy were enrolled in the present study. Clinicopathological characteristics and prognosis of gastric cancer patients with well, moderately and poorly differentiation status were analyzed.

          Results

          There were 2422 male (78.4%) and 668 female (21.6%). The median age was 58 (20–90) years. There were 370 (12.0%) well differentiated tumors, 836 (27.0%) moderately differentiated tumors and 1884 (61.0%) poorly differentiated tumors. Well and moderately differentiation status were associated with older age, male gender, smaller tumor, shallower invasion, less lymph node involvement and earlier tumor stage (all p < 0.001). Inversely, poorly differentiation status was associated with younger age, female gender, larger tumor, deeper invasion, more lymph node involvement and later tumor stage (all p < 0.001). With respect to prognosis, well differentiation status was associated with favorable overall survival and poorly differentiation status was associated with unfavorable overall survival ( p < 0.001). However, after matching with age, tumor size, T and N stage, there was no significant difference among the overall survival of the three groups ( p = 0.415).

          Conclusions

          Well, moderately and poorly differentiation status was significantly associated with clinicopathological features of gastric cancer patients. However, it was not associated with the prognosis of gastric cancer patients.

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          Most cited references20

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          Review article: the epidemiology and prevention of gastric cancer.

          K Fock (2014)
          Gastric cancer can be divided into cardia and noncardia gastric adenocarcinoma (NCGA). Non cardia gastric cancer is a disease that has declined in global incidence but has remained as an extremely lethal cancer. To review recent advances in epidemiology and strategies in prevention of non cardia gastric cancer. A rapid literature search strategy was developed for all English language literature published before March 2013. The search was conducted using the electronic databases PubMed and EMBASE. The search strategy included the keywords 'stomach neoplasms', 'gastric cancer', 'epidemiology', 'risk factor', 'early detection of cancer', 'mass screening', 'cancer burden', 'prevention' and 'cost-effectiveness'. The search strategy was adjusted according to different requirements for each database. The specific search was also performed in cancer-related websites for country-specific information. The search was limited to past 10 years. Gastric cancer is the fifth most common cancer but the third leading cause of cancer death. The case fatality rate is 75%. Screening by radiological or endoscopic methods has limited success in prevention of gastric cancer. Helicobacter pylori has been identified as a carcinogen, accounting for 60-70% of gastric cancer globally and eradication is a potential preventive measure. A meta-analysis in 2009 demonstrated that individuals treated with H. pylori eradication therapy can reduce gastric cancer risk. The extended Shandong Intervention trial that lasted 14.3 years showed that H. pylori eradication therapy significantly reduced gastric cancer incidence by 39%. Consensus groups from Asia, Europe and Japan have recommended H. pylori eradication as primary prevention in high-risk areas. Following eradication therapy, endoscopic surveillance of pre-malignant lesions using enhanced imaging appears to be another promising preventive strategy. Gastric cancer remains a major diagnostic and therapeutic challenge. There is emerging evidence that H. pylori eradication in high gastric cancer regions can lead to a decline in the incidence of this highly lethal disease. © 2014 John Wiley & Sons Ltd.
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            Hypoxia-induced dedifferentiation of tumor cells--a mechanism behind heterogeneity and aggressiveness of solid tumors.

            Histopathological examination of solid tumors frequently reveals pronounced tumor cell heterogeneity with regards to cell organization, cell morphology, cell size, nuclei morphology, etc. Analyses of gene expression patterns by immunohistochemistry or in situ hybridization techniques further strengthen the actual presence of phenotypic heterogeneity, often demonstrating substantial diversity within a given tumor. The molecular mechanisms underlying the phenotypic heterogeneity are very complex with genetic, epigenetic and environmental components. Hypoxia, shortage in oxygen, greatly influences cellular phenotypes by altering the expression of specific genes, and is an important contributor to intra- and inter-tumor cell diversity as revealed by the pronounced but non-uniform expression of hypoxia-driven genes in solid tumors (reviewed in [Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3:721-32; Harris AL. Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer 2002;2:38-47.]). The oxygen pressure in solid tumors is generally lower than in the surrounding non-malignant tissues, and tumors exhibiting extensive hypoxia have been shown to be more aggressive than corresponding tumors that are better oxygenized [Vaupel P. Oxygen transport in tumors: characteristics and clinical implications. Adv Exp Med Biol 1996;388:341-51; Vaupel P, Thews O, Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 2001;18:243-59.]. We recently observed that hypoxic neuroblastoma cells and breast cancer cells lose their differentiated gene expression patterns and develop stem cell-like phenotypes [Jögi A, Øra I, Nilsson H, Lindeheim A, Makino Y, Poellinger L, et al. Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci USA 2002;99:7021-6; Helczynska K, Kronblad A, Jögi A, Nilsson E, Beckman S, Landberg G, et al. Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ. Cancer Res 2003;63:1441-4.]. As low stage of differentiation in neuroblastoma and in breast cancer is linked to poor prognosis, hypoxia-induced dedifferentiation will not only contribute to tumor heterogeneity but could also be one mechanism behind increased aggressiveness of hypoxic tumors. The effect(s) of hypoxia on tumor cell differentiation status is the focus of this review.
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              Stage-stratified prognosis of signet ring cell histology in patients undergoing curative resection for gastric adenocarcinoma.

              The prognosis of signet ring cell (SRC) gastric adenocarcinoma is regarded as poor, although studies addressing outcomes in relation to non-SRC tumors are conflicting. Our objective was to compare the survival of SRC tumors with stage-matched intestinal-type tumors in a cohort of Western patients.
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                Author and article information

                Contributors
                +86-029-84771531 , zhanghwfmmu@126.com
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                3 September 2018
                3 September 2018
                2018
                : 18
                : 865
                Affiliations
                [1 ]ISNI 0000 0004 1761 4404, GRID grid.233520.5, Division of Digestive Surgery, , Xijing Hospital of Digestive Diseases, Fourth Military Medical University, ; 127 West Changle Road, Xi’an, 710032 Shaanxi China
                [2 ]Cadre’ s sanitarium, 62101 Army of PLA, 67 Nahu Road, Xinyang, 464000 Henan China
                [3 ]Department of General Surgery, No. 534 Hospital of PLA, Yingzhou Road, Luoyang, 471000 Henan China
                [4 ]Department of General Surgery, No. 91 Hospital of PLA, 239Gongye Road, Jiaozuo, 454000 Henan China
                Author information
                http://orcid.org/0000-0002-9971-4518
                Article
                4780
                10.1186/s12885-018-4780-0
                6122741
                30176846
                c8d28e68-958b-4722-9e70-d5b09444fd7a
                © The Author(s). 2018

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                History
                : 5 December 2017
                : 28 August 2018
                Funding
                Funded by: National Natural Scientific Foundation of China
                Award ID: 31100643
                Award ID: 31570907
                Award ID: 81300301
                Award ID: 81572306
                Award ID: 81502403
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                gastric cancer,differentiation status,clinicopathological characteristics,prognosis

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