Construction of tumor infiltrating lymphocyte score in patients with gastric cancer and its relationship with prognosis
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摘要: 目的:构建胃癌患者肿瘤浸润淋巴细胞(TIL)评分,并探讨其与患者预后的关系。方法:选取2015年3月—2016年3月进行胃切除手术的患者523例,收集胃癌组织标本,采用免疫组化方法对胃癌组织标本的组织芯片中的6种淋巴细胞的特征进行分析,依据淋巴细胞特征及其比值分为高表达组和低表达组,通过ROC曲线分析不同TIL浸润情况患者的生存状态。使用6种淋巴细胞的特征及其比值,根据淋巴因子的表达水平构建TIL评分,并对其一致性和可靠性进行评估。523例患者采用计算机产生随机数法以3∶1的比例分为训练集(n=393)和测试集(n=130),将训练集患者TIL评分分为高、低2组,探究TIL评分与胃癌患者临床病理特征的相关性。对患者进行5年随访,通过Logistic回归法对训练集患者的独立预后因素进行探讨,构建列线图预测模型,并对模型进行验证。结果:CD3+、CD4+、CD8+、CD20+、CD57+、FOXP3+浸润免疫细胞和部分临床病理特征之间呈显著负相关性,浸润程度越大,患者的生存率越高。构建的TIL评分与胃癌患者临床病理特征之间存在相关性,高TIL评分的患者肿瘤相对较小,肿瘤浸润深度相对较浅,淋巴结转移相对较少以及TNM分期相对更早,差异有统计学意义(P<0.05)。单因素和多因素Logistic回归分析结果显示,肿瘤大小、TNM分期、肿瘤分化程度和TIL评分均为胃癌患者预后的影响因素(P<0.05),基于训练集独立预后因素构建的列线图模型具有良好的预测准确性。结论:CD3+、CD4+、CD8+、CD20+、CD57+、FOXP3+浸润免疫细胞和部分临床病理特征之间呈显著负相关性,通过单一的TIL的特征及其比值建立的综合性指标TIL评分可用于预测胃癌患者的预后,整合TIL评分和临床危险因素构建的列线图预测模型对于胃癌患者的预后具有较高的预测价值。Abstract: Objective: To construct tumor infiltrating lymphocyte(TIL) score in patients with gastric cancer and explore its relationship with prognosis.Methods: We selected 523 patients who underwent gastrectomy from March 2015 to March 2016, collected gastric cancer tissue samples, and analyzed the characteristics of 6 types of lymphocytes in the tissue microarray of gastric cancer tissue samples using immunohistochemical methods. The characteristics of lymphocytes and their ratios were divided into high expression group and low expression group, and the survival status of patients with different TIL infiltration conditions was analyzed by ROC curve. Using the characteristics of the 6 lymphocytes and their ratios, the TIL-score was constructed based on the expression levels of lymphokines, and its consistency and reliability were evaluated. Five hundred twenty-three patients were divided into training set(n=393) and test set(n=130) at a ratio of 3∶ 1 using computer-generated random number method. The TIL-score was divided into high and low two groups, and the TIL-score and The correlation of clinicopathological characteristics in patients with gastric cancer. The patients were followed up for 5 years, the independent prognostic factors of the training set patients were explored by Logistic regression method, the nomogram prediction model was constructed, and the model was validated.Results: There is a significant negative correlation between CD3+, CD4+, CD8+, CD20+, CD57+, FOXP3+infiltrating immune cells and some clinicopathological characteristics. The greater the degree of infiltration, the higher the survival rate of patients. There is a correlation between the constructed TIL-score and the clinicopathological characteristics of gastric cancer patients. Patients with high TIL-score have relatively small tumors, relatively shallow depth of tumor invasion, relatively few lymph node metastases, and relatively earlier TNM staging. Statistically significant(P<0.05). After 5 years of follow-up, the logistic regression method was used to explore the prognostic factors affecting the five-year survival rate of the patients in the training set. The results of univariate and multivariate analysis showed that the tumor size, TNM stage, tumor differentiation degree and TIL-score were all Independent prognostic factors(P<0.05). The nomogram model constructed based on the independent prognostic factors of the training set has good prediction accuracy.Conclusion: There is a significant negative correlation between CD3+, CD4+, CD8+, CD20+, CD57+, FOXP3+infiltrating immune cells and some clinicopathological characteristics. The comprehensive index TIL-score established by several single TIL characteristics and their ratios can be used to predict gastric cancer For the prognosis of patients, the nomogram prediction model constructed by integrating TIL-score and clinical risk factors has high predictive value for the prognosis of patients with gastric cancer.
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Key words:
- tumor infiltrating lymphocyte /
- stomach cancer /
- prognosis /
- five-year survival rate
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