Abstract
BackgroundGiven the complexity of tumor microenvironment, no single marker from cancer cells could adequately predict the clinical outcomes of gastric cancer (GC). The objective of this study was to evaluate the prognostic role of combined features including conventional pathology, proteinase and immune data in GC.MethodsIn addition to pathological studies, immunohistochemistry was used to assess membrane-type 1 matrix metalloproteinase (MT1-MMP) expression and CD11b + immunocytes density in three independent GC tissue microarrays containing 184 GC tissues. Separate and combined features were evaluated for their impact on overall survival (OS).ResultsWe found that traditional factors including tumor size, histological grade, lymph node status, serosa invasion and TNM stage were associated with OS (P < 0.05 for all). Moreover, statistically significant differences in OS were found among lymph node ratio (LNR) subgroups (P < 0.001), MT1-MMP subgroups (P = 0.015), and CD11b + immunocytes density subgroups (P = 0.031). Most importantly, combined feature (MT1-MMP positive, low CD11b + immunocytes density and high LNR) was found by multivariate analysis to be an independent prognostic factors for OS after excluding other confounding factors (HR = 3.818 [95%CI: 2.223-6.557], P < 0.001). In addition, this combined feature had better performance in predicting clinical outcomes after surgery long before recurrence had occurred (Area under the curve: 0.689 [95%CI: 0.609-0.768], P < 0.001).ConclusionsThese findings indicate that better information on GC prognosis could be obtained from combined clinico-pathological factors, tumor cells and the tumor microenvironment.
Highlights
Given the complexity of tumor microenvironment, no single marker from cancer cells could adequately predict the clinical outcomes of gastric cancer (GC)
Immunohistochemistry was performed in all GC tissue microarrays (TMAs) and the result of each specimen was obtained for images-based digital analysis (Figure 1A-1D)
CD11b + immunocytes mainly infiltrated into the juncture of cancer nest and stromal (Figure 1F, 1H)
Summary
Given the complexity of tumor microenvironment, no single marker from cancer cells could adequately predict the clinical outcomes of gastric cancer (GC). A new prognostic tool of lymph node ratio (LNR), defined as the number of MLN divided by the number of lymph nodes retrieved, was proposed It can improve the prognosis accuracy and reduce the stage migration when compared with the UICC (2002, 6th edition) staging system [6,7]. The discovery of other socalled promising markers in laboratory translates rather slowly into clinical applicability One reason for this is the fact that cancer development and progression is determined by the co-evolution between tumor cells and tumor microenvironment rather than a single mutation [9]. Screening new molecular factors from the complex tumor microenvironment (cellular and stromal components) represents another essential approach to identify prognostic factors
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