Liu Kai, Yang Kun, Wu Bin, Chen HaiNing, Chen XiaoLong, Chen XinZu, Jiang LiLi, Ye FuXiang, He Du, Lu ZhengHao, Xue Lian, Zhang WeiHan, Li Qiu, Zhou ZongGuang, Mo XianMing, Hu JianKun
From the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China (KL,KY, BW,HC, XC, XC, LX, WZ, ZZ, JH); Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China (KL,KY, BW,HC, XC, XC, LX, WZ, JH); Department of Pathology, West China Hospital, Sichuan University, China (LJ, DH); Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (FY); Department of Oncology, West China Hospital, Sichuan University, China (QL); and Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China (XM).
Medicine (Baltimore). 2015 Sep;94(39):e1631. doi: 10.1097/MD.0000000000001631.
Immune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear. We determined the prognostic significance of different immune cells in intratumoral tissue (T), stromal tissue (S), and adjacent normal tissue (N) of 166 gastric cancer cases and their interactions, including CD3+, CD4+, CD8, CD57+, CD68+, CD66b+, and Foxp3+ cells, and established an effective prognostic nomogram based on the immune reactions. We found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio, TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+ ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high TCD57+/SCD57+ ratio, TCD66b+/SCD66b+ ratio, SCD8+/SFoxp3+ ratio, and TFoxp3+/NFoxp3+ ratio were associated with significantly worse outcome. Multivariate analysis indicated that tumor size, longitudinal tumor location, N stage, TCD68+/SCD68+ ratio, TCD8+/TFoxp3+ ratio, density of TFoxp3+ cells, and TCD66b+/SCD66b+ ratio were independent prognostic factors, which were all selected into the nomogram. The calibration curve for likelihood of survival demonstrated favorable consistency between predictive value of the nomogram and actual observation. The C-index (0.83, 95% CI: 0.78 to 0.87) of our nomogram for predicting prognosis was significantly higher than that of TNM staging system (0.70). Collectively, high TCD68+/SCD68+ ratio and TCD8+/TFoxp3+ ratio were associated with improved overall survival, whereas high density of TFoxp3+ cells and TCD66b+/SCD66b+ ratio demonstrated poor overall survival, which are promising independent predictors for overall survival in gastric cancer.
免疫细胞有助于确定胃癌的预后。然而，它们的确切作用尚不清楚。我们确定了166例胃癌病例的肿瘤内组织（T）、基质组织（S）和邻近正常组织（N）中不同免疫细胞的预后意义及其相互作用，包括CD3⁺、CD4⁺、CD8、CD57⁺、CD68⁺、CD66b⁺和Foxp3⁺细胞，并基于免疫反应建立了有效的预后列线图。我们发现TCD3⁺、TCD4⁺、TCD8⁺、SCD3⁺、SCD4⁺、SCD57⁺、SCD66b⁺和NFoxp3⁺细胞的高密度，以及高TCD8⁺/SCD8⁺比值、TCD68⁺/SCD68⁺比值、TCD3⁺/TFoxp3⁺比值、TCD4⁺/TFoxp3⁺比值、TCD8⁺/TFoxp3⁺比值、SCD3⁺/SFoxp3⁺比值和SCD4⁺/SCD8⁺比值与更好的生存率相关，而TCD66b⁺、TFoxp3⁺、SFoxp3⁺和NCD66b⁺细胞的高密度以及高TCD57⁺/SCD57⁺比值、TCD66b⁺/SCD66b⁺比值、SCD8⁺/SFoxp3⁺比值和TFoxp3⁺/NFoxp3⁺比值与显著更差的预后相关。多因素分析表明，肿瘤大小、肿瘤纵向位置、N分期、TCD68⁺/SCD68⁺比值、TCD8⁺/TFoxp3⁺比值、TFoxp3⁺细胞密度和TCD66b⁺/SCD66b⁺比值是独立的预后因素，均被纳入列线图。生存可能性的校准曲线显示列线图的预测值与实际观察之间具有良好的一致性。我们的预后列线图预测预后的C指数（0.83，95%CI：0.78至0.87）显著高于TNM分期系统（0.70）。总体而言，高TCD68⁺/SCD68⁺比值和TCD8⁺/TFoxp3⁺比值与改善的总生存期相关，而TFoxp3⁺细胞的高密度和TCD66b⁺/SCD66b⁺比值表明总生存期较差，它们是胃癌总生存期有前景且独立的预测指标。
