循环细胞因子在化疗难治性结直肠癌中的预后价值

Prognostic Value of Circulating Cytokines in Chemorefractory Colorectal Cancer.

作者信息

Assaf Irene, Fimereli Danai, Anthoine Geraldine, Fazio Roberta, Daprà Valentina, Audisio Alessandro, Bardiaux Alina, Telli Tugba Akin, Vanhooren Michele, Saude-Conde Rita, Bregni Giacomo, Hendlisz Alain, Sclafani Francesco

机构信息

Department of Digestive Oncology, Institut Jules Bordet, The Brussels University Hospital, 1070 Brussels, Belgium.

Breast Cancer Translational Laboratory, Institut Jules Bordet, The Brussels University Hospital, 1070 Brussels, Belgium.

出版信息

Cancers (Basel). 2023 Dec 13;15(24):5823. doi: 10.3390/cancers15245823.

DOI:10.3390/cancers15245823

PMID:38136368

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10742027/

Abstract

Circulating cytokines could be optimal biomarkers for prognostication and management decisions in colorectal cancer (CRC). Chemorefractory CRC patients with available plasma samples were included in this study. In the discovery cohort ( = 85), 182 circulating cytokines were tested with a semi-quantitative multiplex assay, and prognostic cytokines were analyzed in the validation cohort ( = 111) by ELISA. Overall survival (OS) was the primary outcome measure, with the false discovery rate (FDR) method (significance level of <0.01) being used to correct for multiple comparisons. Four cytokines were associated with OS in the discovery cohort: insulin-like growth factor-binding protein 1 (IGFBP-1) (HR 2.1 [95%CI: 1.58-2.79], FDR < 0.001), insulin-like growth factor-binding protein 2 (IGFBP-2) (HR 1.65 [95%CI: 1.28-2.13], FDR = 0.006), serum amyloid A (SAA) (HR 1.84 [95%CI: 1.39-2.43], FDR < 0.001), and angiotensin II (HR 1.65 [95%CI: 1.29-2.1], FDR = 0.006). Of these, IGFBP-1 (HR 2.70 [95%CI: 1.56-4.76], FDR = 0.007) and IGFBP-2 (HR 3.33 [95%CI: 1.64-6.67], FDR = 0.008) were confirmed to be independently associated with OS in the validation cohort. Patients with high concentrations of IGFBP-1 and/or IGFBP-2 had a median OS of 3.0 months as compared with 6.9 months for those with low concentrations of both cytokines (HR 2.44 [95%CI: 1.52-4.0], FDR = 0.002) Validation of circulating IGFBP-1 and IGFBP-2 as independent prognostic biomarkers for chemorefractory CRC in larger, independent series is warranted.

摘要

循环细胞因子可能是结直肠癌（CRC）预后评估和治疗决策的最佳生物标志物。本研究纳入了有可用血浆样本的化疗难治性CRC患者。在发现队列（n = 85）中，采用半定量多重检测法检测了182种循环细胞因子，并在验证队列（n = 111）中通过酶联免疫吸附测定法（ELISA）分析了预后细胞因子。总生存期（OS）是主要结局指标，采用错误发现率（FDR）方法（显著性水平<0.01）校正多重比较。在发现队列中，有四种细胞因子与OS相关：胰岛素样生长因子结合蛋白1（IGFBP-1）（风险比[HR] 2.1 [95%置信区间：1.58 - 2.79]，FDR < 0.001）、胰岛素样生长因子结合蛋白2（IGFBP-2）（HR 1.65 [95%置信区间：1.28 - 2.13]，FDR = 0.006）、血清淀粉样蛋白A（SAA）（HR 1.84 [95%置信区间：1.39 - 2.43]，FDR < 0.001）和血管紧张素II（HR 1.65 [95%置信区间：1.29 - 2.1]，FDR = 0.006）。其中，IGFBP-1（HR 2.70 [95%置信区间：1.56 - 4.76]，FDR = 0.007）和IGFBP-2（HR 3.33 [95%置信区间：1.64 - 6.67]，FDR = 0.008）在验证队列中被证实与OS独立相关。IGFBP-1和/或IGFBP-2浓度高的患者中位OS为3.0个月，而两种细胞因子浓度低的患者为6.9个月（HR 2.44 [95%置信区间：1.52 - 4.0]，FDR = 0.002）。有必要在更大规模的独立队列中验证循环IGFBP-1和IGFBP-2作为化疗难治性CRC独立预后生物标志物的作用。