title: Prognostic value of pre-operative inflammatory response biomarkers in gastric cancer patients and the construction of a predictive model.
abstract: BACKGROUND
  Inflammation plays an integral role in carcinogenesis and tumor progression. Inflammatory response biomarkers have shown to be promising prognostic factors for improving the predictive accuracy in various cancers. The aim of this study is to investigate the prognostic significance of pre-operative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in gastric cancer (GC).
  
  
  METHODS
  389 patients who had undergone gastrectomy were enrolled from 2007 to 2009 in this study. NLR, dNLR, PLR and LMR were calculated from peripheral blood cell count taken at pre-operation. Receiver operating curve (ROC) was used to determine the optimal cut-off levels for these biomarkers. A predictive model or nomogram was established to predict prognosis for cancer-specific survival (CSS) and disease-free survival (DFS), and the predictive accuracy of the nomogram was determined by concordance index (c-index).
  
  
  RESULTS
  The median follow-up period was 24 months ranging from 3 months to 60 months. The optimal cut-off levels were 2.36 for NLR, 1.85 for dNLR, 132 for PLR and 4.95 for LMR by ROC curves analysis. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), CSS and DFS, however, elevated LMR showed an adverse effect on worse OS, CSS and DFS. Multivariate analysis revealed that elevated dNLR was an independent factor for worse OS, and NLR was superior to dNLR, PLR and LMR in terms of hazard ratio (HR = 1.53, 95% CI = 1.11-2.11, P = 0.010), which was shown to be independent prognostic indicators for both CSS and DFS. Moreover, the nomogram could more accurately predict CSS (c-index: 0.89) and DFS (c-index: 0.84) in surgical GC patients.
  
  
  CONCLUSIONS
  Pre-operative NLR and dNLR may serve as potential prognostic biomarkers in patients with GC who underwent surgical resection. The proposed nomograms can be used for the prediction of CSS and DFS in patients with GC who have undergone gastrectomy.
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. qiw_deng@163.com.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. 1061851556@qq.com.
authors.forename: Bangshun
authors.initials: B
authors.lastname: He
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. 2697250365@qq.com.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Huai'an Second People's Hospital, Huai'an, Jiangsu, China. jinjun_hou@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Yue
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. 570154244@qq.com.|Medical college, Southeast University, Nanjing, Jiangsu, China. 570154244@qq.com.
authors.forename: Houqun
authors.initials: H
authors.lastname: Ying
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. 2339820358@qq.com.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. sunhuiling1988@yeah.net.|Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China. sunhuiling1988@yeah.net.
authors.forename: Huiling
authors.initials: H
authors.lastname: Sun
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. tiany_gao@163.com.|Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China. tiany_gao@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. 18262638632@139.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. love857_qiwendeng@163.com.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Orthopaedics, Lanxi People's Hospital, Jinhua, Zhejiang, China. 303794458@qq.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China. shukwang@163.com.
authors.forename: Shukui
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D011300:Preoperative Care; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*
chemical_list: D014408:Biomarkers, Tumor