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尿白细胞介素-6和白细胞介素-8作为膀胱尿路上皮癌的预测标志物:一项初步研究。

Urinary IL-6 and IL-8 as predictive markers in bladder urothelial carcinoma: A pilot study.

作者信息

VandenBussche Christopher J, Heaney Christopher D, Kates Max, Hooks John J, Baloga Kelly, Sokoll Lori, Rosenthal Dorothy, Detrick Barbara

机构信息

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

出版信息

Cancer Cytopathol. 2024 Jan;132(1):50-59. doi: 10.1002/cncy.22767. Epub 2023 Oct 9.

Abstract

BACKGROUND

Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear.

METHODS

Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL-8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL-6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations.

RESULTS

Significantly elevated concentrations of IL-6 and IL-8 were detected in the urine from patients with urothelial carcinoma on follow-up compared to patients with benign follow-up. The presence of both IL-6 and IL-8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow-up. The presence of the combination of both IL-6 and IL-8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL-6 and IL-8 concentrations in the urine from patients with HGUC vs. the hematuria cohort.

CONCLUSIONS

The presence of IL-6 and IL-8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory.

摘要

背景

细胞因子是众多恶性肿瘤中的关键因素,在肿瘤微环境中发挥重要调节作用。人们对了解细胞因子如何调节肿瘤微环境以及哪些细胞因子可作为肿瘤进程的标志物的兴趣与日俱增;然而,膀胱癌中细胞因子全貌仍不明确。

方法

随机间隔收集足量新鲜尿液标本。使用市售标准酶免疫测定法测定尿液中白细胞介素-8(CXCL8)、CCL18和CXCL9的浓度。使用高灵敏度酶免疫测定试剂盒测定尿液中白细胞介素-6的浓度。尿细胞因子浓度用尿肌酐浓度进行标准化。

结果

与良性随访患者相比,随访时尿路上皮癌患者尿液中白细胞介素-6和白细胞介素-8浓度显著升高。与良性随访患者的样本相比,高级别尿路上皮癌(HGUC)队列尿液样本中同时存在白细胞介素-6和白细胞介素-8显示出明显的区分度。白细胞介素-6和白细胞介素-8同时存在的敏感度为90.0%,特异度为81.25%。对HGUC患者与血尿队列患者尿液中白细胞介素-6和白细胞介素-8浓度进行受试者操作特征分析时,也获得了类似数据。

结论

尿液标本中白细胞介素-6和白细胞介素-8的存在可能对尿路上皮癌具有预测价值。然而,需要进行大规模纵向研究以统计学方式消除混杂因素并支持这一理论。

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