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      Application of preoperative artificial neural network based on blood biomarkers and clinicopathological parameters for predicting long-term survival of patients with gastric cancer

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          Abstract

          BACKGROUND

          Because of the powerful abilities of self-learning and handling complex biological information, artificial neural network (ANN) models have been widely applied to disease diagnosis, imaging analysis, and prognosis prediction. However, there has been no trained preoperative ANN (preope-ANN) model to preoperatively predict the prognosis of patients with gastric cancer (GC).

          AIM

          To establish a neural network model that can predict long-term survival of GC patients before surgery to evaluate the tumor condition before the operation.

          METHODS

          The clinicopathological data of 1608 GC patients treated from January 2011 to April 2015 at the Department of Gastric Surgery, Fujian Medical University Union Hospital were analyzed retrospectively. The patients were randomly divided into a training set (70%) for establishing a preope-ANN model and a testing set (30%). The prognostic evaluation ability of the preope-ANN model was compared with that of the American Joint Commission on Cancer (8 th edition) clinical TNM (cTNM) and pathological TNM (pTNM) staging through the receiver operating characteristic curve, Akaike information criterion index, Harrell's C index, and likelihood ratio chi-square.

          RESULTS

          We used the variables that were statistically significant factors for the 3-year overall survival as input-layer variables to develop a preope-ANN in the training set. The survival curves within each score of the preope-ANN had good discrimination ( P < 0.05). Comparing the preope-ANN model, cTNM, and pTNM in both the training and testing sets, the preope-ANN model was superior to cTNM in predictive discrimination (C index), predictive homogeneity (likelihood ratio chi-square), and prediction accuracy (area under the curve). The prediction efficiency of the preope-ANN model is similar to that of pTNM.

          CONCLUSION

          The preope-ANN model can accurately predict the long-term survival of GC patients, and its predictive efficiency is not inferior to that of pTNM stage.

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          Most cited references25

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          Role of systemic inflammatory response in predicting survival in patients with primary operable cancer.

          Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Glasgow Prognostic Score, the neutrophil:lymphocyte ratio and the platelet:lymphocyte ratio. This review demonstrates that there is now good evidence that preoperative measures of the systemic inflammatory response predict cancer survival, independent of tumor stage, in primary operable cancer. The evidence is particularly robust in colorectal (including liver metastases), gastro-esophageal and renal cancers. As described in this article, measurement of the systemic inflammatory response is simple, reliable and can be clinically incorporated into current staging algorithms. This will provide the clinician with a better prediction of outcome, and therefore better treatment allocation in patients with primary operable cancer. Furthermore, systemic inflammation-based markers and prognostic scores not only identify patients at risk, but also provide well-defined therapeutic targets for future clinical trials.
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            Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis

            Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy.
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              High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer.

              The neutrophil-lymphocyte ratio (NLR) reflects inflammatory status. An elevated NLR has been reported to be a prognostic indicator in some malignant tumors. The aim of this study was to evaluate the clinical significance of the preoperative NLR in patients with primary gastric cancer. A total of 709 men and 319 women, with a mean age of 64.4 years, who underwent gastrectomy were included. The numbers of patients in each pathological stage were as follows: stage I, 584; stage II, 132; stage III, 153; and stage IV, 159. The mean NLR was 2.62 +/- 1.68. A total of 127 patients (12.4%) with an NLR of 4.0 or more were classified as high NLR individuals in this study. The prognostic significance of a high NLR, together with various clinicopathological factors, was evaluated by multivariate analysis. The 5-year survival of patients with a high NLR was significantly worse than that of patients with a low NLR (57% vs 82%, P < 0.001). Univariate and multivariate analyses of clinicopathological factors affecting survival revealed that high NLR, depth of tumor, positive lymph nodes, distant metastasis, peritoneal metastasis, poorly differentiated type, and high platelet count were significant risk factors for reduced survival. On multivariate analysis, after adjusting for tumor stage, a high NLR was an independent risk factor for reduced survival (P = 0.003; adjusted hazard ratio, 1.845; 95% confidence interval, 1.236-2.747). A high preoperative NLR may be a convenient biomarker to identify patients with a poor prognosis after resection for primary gastric cancer.
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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
                21 November 2019
                21 November 2019
                : 25
                : 43
                : 6451-6464
                Affiliations
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Department of Gastric Surgery and Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
                Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian Province, China
                Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China. xjwhw2019@ 123456163.com
                Author notes

                Author contributions: Que SJ and Chen QY contributed equally to this work. Huang CM, Zheng CH, Chen QY, and Que SJ designed the research; Que SJ, Chen QY, Zhong Q, Liu ZY, Xie JW, Wang JB, Lin JX, Lu J, Cao LL, Lin M, Tu RH, Huang ZN, Lin JL, Zheng HL, Li P, Zheng CH, and Huang CM performed the research; Que SJ, Chen QY, Zhong Q, and Liu ZY contributed new reagents or analytic tools; Que SJ, Chen QY, Zhong Q, Liu ZY, Huang ZN, Lin JL, Zheng HL, Zheng CH, and Huang CM, Li P analyzed the data; Que SJ, Chen QY, Zhong Q, Liu ZY, Huang CM, and Li P wrote the paper.

                Supported by the Scientific and Technological Innovation Joint Capital Projects of Fujian Province, No. 2016Y9031; the Construction Project of Fujian Province Minimally Invasive Medical Center, No. [2017]171; the General Project of Miaopu Scientific Research Fund of Fujian Medical University, No. 2015MP021; the Youth Project of Fujian Provincial Health and Family Planning Commission, No. 2016-1-41; the Fujian Province Medical Innovation Project, Chinese Physicians Association Young Physician Respiratory Research Fund, No. 2015-CXB-16; and the Fujian Science and Technology Innovation Joint Fund Project, No. 2017Y9004.

                Corresponding author: Jian-Wei Xie, MD, PhD, Doctor, Professor, Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29, Xinquan Road, Fuzhou 350001, Fujian Province, China. xjwhw2019@ 123456163.com

                Telephone: +86-591-83363366 Fax: +86-591-83363366

                Article
                jWJG.v25.i43.pg6451
                10.3748/wjg.v25.i43.6451
                6881508
                31798281
                a721f48f-04ce-4070-9396-59e7404c0563
                ©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 August 2019
                : 17 September 2019
                : 17 October 2019
                Categories
                Retrospective Study

                gastric cancer,artificial neural network model,prognostic model,preoperative,blood biomarkers,long-term survival

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