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      Prognostic Value Of Preoperative Systemic Inflammatory Biomarkers In Patients With Gallbladder Cancer And The Establishment Of A Nomogram

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          Abstract

          Background and aim

          Preoperative systemic inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have been developed to predict patient outcome in several types of carcinomas. The aim of this study was to investigate the potential prognostic value of NLR, dNLR, PLR, and LMR, and establish a prognostic nomogram in postoperative GBC patients who underwent radical cholecystectomy.

          Methods

          169 GBC patients were retrospectively enrolled in the present study. ROC curve analysis was used to determine the optimal cut-off values of systemic inflammatory biomarkers. The prognostic value of those biomarkers was investigated according to the Kaplan-Meier method and Cox regression model. A relevant prognostic nomogram was established.

          Results

          Results showed that NLR, dNLR, PLR, and LMR were significantly associated with overall survival (OS); whereas, NLR and LMR were retained as independent indicators. Based on these independent predictors including tumor differentiation, T stage, N stage, CEA, NLR, and LMR, a nomogram was generated with an accuracy of 0.801.

          Conclusion

          Based on our findings, the predictive nomogram could accurately predict individualized survival probability of postoperative GBC patients, and might support clinicians in treatment optimization and clinical decision-making.

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          Most cited references31

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          Neutrophils in cancer: neutral no more.

          Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets.
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            Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

            Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.
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              Preface

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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                CMAR
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                21 October 2019
                2019
                : 11
                : 9025-9035
                Affiliations
                [1 ]Department of Hepatobiliary Surgery, Jing Zhou Central Hospital, The Second Clinical Medical College, Yangtze University , Jing Zhou, Hubei 434020, People’s Republic of China
                [2 ]Department of Ophthalmology, Jing Zhou Central Hospital, The Second Clinical Medical College, Yangtze University , Jing Zhou, Hubei 434020, People’s Republic of China
                Author notes
                Correspondence: Shuai Wang; Zhen-Gang Sun Department of Hepatobiliary Surgery, Jing Zhou Central Hospital, The Second Clinical Medical College, Yangtze University , Jing Zhou, Hubei434020, People’s Republic of ChinaTel +86-18107167230 Email wsjoy@163.com; 669210966@qq.com
                Article
                218119
                10.2147/CMAR.S218119
                6814315
                31695494
                bfef4809-0f68-48b7-a1a2-9aeae02e0770
                © 2019 Deng et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 03 June 2019
                : 16 September 2019
                Page count
                Figures: 4, Tables: 3, References: 48, Pages: 11
                Categories
                Original Research

                Oncology & Radiotherapy
                gallbladder carcinoma,systemic inflammatory biomarker,prognosis,overall survival,nomogram

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