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      Relationship between Inflammatory and Biological Markers and Lung Cancer

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          Abstract

          We seek to define inflammatory markers, lipid and protein profiles that may aid in distinguishing lung cancer cases from those who are healthy and to determine the relationships between these levels and cancer stage and cell type. Lung cancer patients ( n = 140, Group 1) and healthy cases ( n = 50, Group 2) were enrolled. We retrieved platelet, platelet-associated markers (plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW)), neutrophil/lymphocyte ratio-NLR, platelet/lymphocyte ratio-PLR, lipids (total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides), proteins (total protein (TP) and albumin), and C-reactive protein (CRP) from electronic records and compared the data from lung cancer patients with those from healthy controls. Platelet, PCT, neutrophil, NLR, PLR, triglycerides, VLDL, and CRP levels were significantly higher in Group 1 compared with Group 2. MPV, lymphocyte, albumin, and HDL levels were significantly lower in Group 1 compared with Group 2. No significant relationship was evident between histopathological types and the level of any marker. Compared to those with early-stage cancer, changes in marker levels in those with advanced-stage cancer were statistically significant. CRP and NLR were significantly higher; albumin and HDL were lower in metastatic patients. We found that platelet, PCT, NLR and PLR, albumin, HDL, and CRP levels aided in lung cancer diagnosis and the detection of late-stage disease. Furthermore, these inflammatory and biological markers are thought to be particularly useful in following the severity of lung cancer.

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          Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer.

          Increasing neutrophil/lymphocyte ratios on preoperative blood tests have been associated with worse survival after resection of colorectal cancer. We sought to determine factors associated with increasing neutrophil/lymphocyte ratios and the stage-adjusted prognostic effect in patients undergoing resection for non-small cell lung cancer. We performed a retrospective review of patients undergoing complete resection for non-small cell lung cancer between 1999 and 2005. Data acquisition was through patient medical records, blood results recorded on admission before surgical intervention, and follow-up by National Health Service database searches and hospital records. Cox proportional hazards regression was used to estimate the effect of neutrophil/lymphocyte ratio on stage-adjusted survival. During the study period, 178 patients underwent pulmonary resection. Of 177 patients, the majority were male 104 (59%), with a mean age of 63 years (standard deviation, 10 years). The median follow-up time was 29 months (interquartile range, 8-56 months), and overall survival was 83% and 54% at 1 and 5 years, respectively. Higher stage was the only factor found to be associated with increasing neutrophil/lymphocyte ratios (P = .019). Total white cell count (P = .990) and neutrophil count (P = .490), age (P = .290), and cell type (P = .490) were not significant predictors of mortality. On multivariable analysis after adjusting for stage, increasing neutrophil/lymphocyte ratios (hazard ratio, 1.10; 95% confidence interval, 1.03-1.17; P = .004) remained an independent prognostic indicator. Increasing preoperative neutrophil/lymphocyte ratios are associated with higher stage but remain an independent predictor of survival after complete resection for primary lung cancer and are a potential biomarker to stratify high risk of death in patients with stage I disease.
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            Prognostic significance of thrombocytosis in patients with primary lung cancer.

            In patients with malignancies, thrombocytosis has previously been related to disease stage, histological type, and survival. In the present study, the prevalence of thrombocytosis and the prognostic information provided by platelet counts were analysed in a large cohort of patients with primary lung cancer. At the time of diagnosis, pretreatment platelet counts were retrospectively recorded in 1,115 consecutive patients with histologically proven primary lung cancer. All patients were reviewed regarding histological type, tumour, node, metastasis (TNM) classification stage and survival. The prevalence of thrombocytosis in patients with lung cancer was compared with that in a series of 550 consecutive out-patients with benign lung disorders. In 269 surgically resected patients, postoperative platelet counts were recorded 1-3 months after resection of the tumour. In the follow-up period, thromboembolic episodes diagnosed either clinically or at autopsy were recorded. The overall prevalence of thrombocytosis (> 400 x 10(9) platelets.L-1) in the patients with lung cancer was 32%. The frequency of thrombocytosis was significantly higher compared with the control subjects (32 vs 6%; p 400 x 10(9) platelets.L-1 greatest in the more advanced TNM stages (stage I and II 23% vs stage III and IV 37%; p < 0.0001). Patients with thrombocytosis had a significantly poorer survival than patients with normal platelet counts (p < 0.0001). In a multivariate survival analysis (Cox model), thrombocytosis continued to correlate strongly with poor survival even when adjusted for histological type, sex, age, and TNM stage (p < 0.001). In surgically resected patients, the frequency of preoperative and postoperative thrombocytosis differed significantly (23.0 vs 8.9%; p < 0.0001). Survival rate was significantly reduced in patients with preoperative thrombocytosis (p = 0.005). Thrombocytosis was not associated with an increased incidence of thromboembolism. In conclusion, thrombocytosis is an independent prognostic factor of survival in patients with primary lung cancer. We suggest that platelet counts should be included in future multivariate analyses of survival in patients with lung cancer.
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              Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice

              Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2–CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                25 June 2018
                July 2018
                : 7
                : 7
                : 160
                Affiliations
                Department of Chest Diseases, University of Health Sciences/Yedikule Chest Disease and Thoracic Surgery Health Practice and Research Center, Istanbul 34760, Turkey; ayse_feyza@ 123456hotmail.com
                Author notes
                [* ]Correspondence: fusunsahin19700@ 123456hotmail.com ; Tel.: +90-532-7112893; Fax: +90-212-5472233
                Author information
                https://orcid.org/0000-0002-8415-2524
                Article
                jcm-07-00160
                10.3390/jcm7070160
                6069225
                29941786
                7b6d6964-32ee-4b4d-bee0-ef450b5df406
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 May 2018
                : 21 June 2018
                Categories
                Article

                lung cancer,neutrophil/lymphocyte ratio,platelet/lymphocyte ratio,biological markers,cancer stage

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