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      Prognostic Significance of EDIL3 Expression and Correlation with Mesenchymal Phenotype and Microvessel Density in Lung Adenocarcinoma

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          Abstract

          We examined the prognostic significance of Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3) expression and its correlations with mesenchymal phenotype and microvessel density in non-small cell lung carcinoma (NSCLC). A total of 268 NSCLC specimens were evaluated retrospectively by immunohistochemical staining for EDIL3, EMT markers (e-cadherin, β-catenin, and vimentin), and CD31 to measure microvessel density. EDIL3, e-cadherin, β-catenin, and vimentin were expressed in 16%, 22.8%, 3.7%, and 10.1% of the specimens, respectively. The mRNA level of EDIL3 in tumor was correlated with the level of EDIL3 protein expression using immunohistochemistry. In lung adenocarcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression, high vimentin expression, and increased microvessel density ( P < 0.001, P = 0.001, and P = 0.023, respectively). In lung squamous cell carcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression and high vimentin expression ( P = 0.021 and P = 0.002, respectively). In lung adenocarcinoma patients, EDIL3 was an independent prognostic factor for overall survival in a multivariate analysis (hazard ratio: 2.552, P = 0.004). EDIL3 is significantly correlated with mesenchymal phenotype, angiogenesis, and tumor progression in lung adenocarcinoma.

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          Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment.

          Leukocyte recruitment to sites of infection or inflammation requires multiple adhesive events. Although numerous players promoting leukocyte-endothelial interactions have been characterized, functionally important endogenous inhibitors of leukocyte adhesion have not been identified. Here we describe the endothelially derived secreted molecule Del-1 (developmental endothelial locus-1) as an anti-adhesive factor that interferes with the integrin LFA-1-dependent leukocyte-endothelial adhesion. Endothelial Del-1 deficiency increased LFA-1-dependent leukocyte adhesion in vitro and in vivo. Del-1-/- mice displayed significantly higher neutrophil accumulation in lipopolysaccharide-induced lung inflammation in vivo, which was reversed in Del-1/LFA-1 double-deficient mice. Thus, Del-1 is an endogenous inhibitor of inflammatory cell recruitment and could provide a basis for targeting leukocyte-endothelial interactions in disease.
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            E-Cadherin/β-Catenin Complex and the Epithelial Barrier

            E-Cadherin/ β -catenin complex plays an important role in maintaining epithelial integrity and disrupting this complex affect not only the adhesive repertoire of a cell, but also the Wnt-signaling pathway. Aberrant expression of the complex is associated with a wide variety of human malignancies and disorders of fibrosis resulting from epithelial-mesenchymal transition. These associations provide insights into the complexity that is likely responsible for the fibrosis/tumor suppressive action of E-cadherin/ β -catenin.
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              Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung

              Invasive mucinous adenocarcinoma is a unique histologic subtype of lung cancer, and our knowledge of its genetic and clinical characteristics is rapidly evolving. Here, we present next- generation sequencing analysis of nucleotide variant and fusion events along with clinical follow-up in a series of lung mucinous adenocarcinoma.
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                Author and article information

                Contributors
                youngwha9556@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                17 August 2017
                17 August 2017
                2017
                : 7
                : 8649
                Affiliations
                [1 ]ISNI 0000 0004 1773 6524, GRID grid.412674.2, Department of Pathology, , College of Medicine, Soonchunhyang University, ; Chonan, Republic of Korea
                [2 ]ISNI 0000 0004 1773 6524, GRID grid.412674.2, , Soonchunhyang medical science research institute, College of medicine, Soonchunhyang University, ; Chonan, Republic of Korea
                [3 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Nuclear Medicine and Molecular Imaging, , Ajou University School of Medicine, ; Suwon, Republic of Korea
                [4 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Thoracic and Cardiovascular Surgery, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                [5 ]ISNI 0000 0004 0532 3933, GRID grid.251916.8, Department of Pathology, , Ajou University School of Medicine, ; Suwon, Republic of Korea
                Article
                8851
                10.1038/s41598-017-08851-9
                5561239
                28819306
                8dbf65ea-f5df-4fa6-855c-5cd4a1e9a737
                © The Author(s) 2017

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 December 2016
                : 14 July 2017
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