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炎症生物标志物在预测输尿管尿路上皮癌患者预后中的临床价值

[Clinical value of inflammatory biomarkers in predicting prognosis of patients with ureteral urothelial carcinoma].

作者信息

Chen H A, Liu S, Li X J, Wang Z, Zhang C, Li F Q, Miao W L

机构信息

Department of Urology, the First Affiliated Hospital, Hebei North Univercity, Zhangjiakou 075061, Hebei, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Mar 26;53(2):302-307. doi: 10.19723/j.issn.1671-167X.2021.02.012.

Abstract

OBJECTIVE

To evaluate the clinical value of inflammation-related markers in predicting the prognosis of patients with ureteral urothelial carcinoma.

METHODS

200 patients with ureteral urothelial carcinoma were randomly divided into two groups by split sample validation: modeling group and validation group. Paraffin embedded pathological specimens of the patients were reviewed. Immunohistochemical method was used to detect tumor-infiltrating neutrophil (TIN) (CD66b), tumor-associated macrophage (TAM) (CD163), lymphocyte (CD, CD4, CD8) counts, peripheral blood neutrophil / lymphocyte ratio (NLR) and tumor tissue neutrophil/monocyte ratio (NMR). According to the results of pathological staging, the patients were divided into non-muscle-invasive and muscle-invasive ureteral urothelial carcinoma group. The resolution of the models was evaluated, and the prognostic nomogram models including only peripheral blood parameters and all parameters were established to compare the accuracy of the two models in predicting the prognosis of patients with urothelial carcinoma of the ureter.

RESULTS

The median follow-up time was 36 months, the progression-free survival was 40 months, and 42 cases (21.0%) showed tumor progression within 3 years. Tumor size, pathological stage and pathological grade were all single-factor variables predicting the first recurrence of ureteral urothelial carcinoma three years after operation. Tumor size, pathological stage, pathological grade, TIN, TAM, NLR and NMR were multi-factor variables predicting the first recurrence three years after operation. Among 104 cases of non-muscle-invasive ureteral urothelial carcinoma, 10 cases (9.6%) recurred for the first time 3 years after operation, 96 cases (33.3%) of muscle invasive ureteral urothelial carcinoma, and the diffe-rence between the two groups was statistically significant (=15.53, < 0.05). The predictive nomogram model of progression free survival was established. The concordance index of progression free survi-val was 0.722 (95%: 0.70-0.78) in non-muscle-invasion group, and 0.725 (95%: 0.71-0.79) in muscle-invasion group, which was in good agreement with the observed 3-year survival rate. The results of discrimination test showed that the concordance index of the whole parameter prediction model of ureteral urothelial carcinoma was 0.726, which was higher than that of peripheral blood parameters (consistency index 0.672). The immune microenvironment of ureteral urothelial carcinoma improved the prediction accuracy of the model.

CONCLUSION

The prognosis prediction model based on immune inflammation-related markers was established as a perfection and supplement for the existing pathological grading and staging system, providing a basis for accurate individualized treatment of patients with urete-ral urothelial carcinoma. The prognosis prediction model based on the relevant indicators of peripheral blood samples is established, which is easy to obtain specimens, and the detection method is simple and economical, which is more conducive to clinical application.

摘要

目的

评估炎症相关标志物在预测输尿管尿路上皮癌患者预后中的临床价值。

方法

采用样本拆分验证法将200例输尿管尿路上皮癌患者随机分为两组:建模组和验证组。回顾性分析患者的石蜡包埋病理标本。采用免疫组织化学方法检测肿瘤浸润中性粒细胞(TIN)(CD66b)、肿瘤相关巨噬细胞(TAM)(CD163)、淋巴细胞(CD、CD4、CD8)计数、外周血中性粒细胞/淋巴细胞比值(NLR)和肿瘤组织中性粒细胞/单核细胞比值(NMR)。根据病理分期结果,将患者分为非肌层浸润性和肌层浸润性输尿管尿路上皮癌组。评估模型的分辨能力,建立仅包含外周血参数和所有参数的预后列线图模型,比较两种模型预测输尿管尿路上皮癌患者预后的准确性。

结果

中位随访时间为36个月,无进展生存期为40个月,42例(21.0%)在3年内出现肿瘤进展。肿瘤大小、病理分期和病理分级均为预测输尿管尿路上皮癌术后3年首次复发的单因素变量。肿瘤大小、病理分期、病理分级、TIN、TAM、NLR和NMR为预测术后3年首次复发的多因素变量。104例非肌层浸润性输尿管尿路上皮癌患者中,10例(9.6%)术后3年首次复发,96例肌层浸润性输尿管尿路上皮癌患者中,33.3%复发,两组差异有统计学意义(=15.53,<0.05)。建立了无进展生存期的预测列线图模型。非肌层浸润组无进展生存期的一致性指数为0.722(95%:0.70 - 0.78),肌层浸润组为0.725(95%:0.71 - 0.79),与观察到的3年生存率吻合良好。判别试验结果显示,输尿管尿路上皮癌全参数预测模型的一致性指数为0.726,高于外周血参数(一致性指数0.672)。输尿管尿路上皮癌的免疫微环境提高了模型的预测准确性。

结论

基于免疫炎症相关标志物的预后预测模型作为对现有病理分级和分期系统的完善和补充而建立,为输尿管尿路上皮癌患者的精准个体化治疗提供依据。建立了基于外周血样本相关指标的预后预测模型,该模型标本获取容易,检测方法简单经济,更有利于临床应用。

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