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弥漫性大B细胞淋巴瘤血清细胞因子谱的评估及其预后意义

Assessment and prognostic significance of a serum cytokine panel in diffuse large B‑cell lymphoma.

作者信息

Xie Shufang, Zhu Lifen, Wang Lei, Wang Shibing, Tong Xiangmin, Ni Wanmao

机构信息

The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China.

Cancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.

出版信息

Oncol Lett. 2024 Mar 28;27(5):237. doi: 10.3892/ol.2024.14370. eCollection 2024 May.

Abstract

The objective of the present study was to assess the levels of circulating cytokines in patients with diffuse large B-cell lymphoma (DLBCL), and to examine the associations between the cytokine levels, clinicopathological manifestations and patient prognosis. The study enrolled 49 patients with DLBCL, 11 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and 67 healthy controls from Zhejiang Provincial People's Hospital (Hangzhou, China) between January 2017 and January 2020. The serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were measured using flow cytometry. The IL-6, IL-10 and IFN-γ levels were significantly raised in patients with DLBCL compared with those in the healthy controls (P<0.05). The levels of IL-10 were significantly higher in patients with raised levels of circulating lactate dehydrogenase (P<0.05), while increases in both IL-6 and IL-10 were associated with raised C-reactive protein (CRP) levels, with IL-6 levels positively associated with those of serum CRP (P<0.01; r=0.66). Additionally, International Prognostic Index (IPI) risk stratification of patients with DLBCL was strongly associated with circulating IL-6 and IL-10 levels. Raised IL-6, IL-10 and TNF-α levels were linked with worse short-term treatment efficacies (P<0.05). Moreover, the accuracy of the model predicting short-term treatment response in patients with DLBCL, obtained using the support vector machine algorithm, was 81.63%. It was also found that raised serum IL-6 and IL-10 levels, together with reduced levels of IL-17, were associated with survival of <1 year in patients with DLBCL (P<0.05), although no significant link was found between cytokine levels and long-term overall survival. In conclusion, the serum levels of IL-6, IL-10, IL-17, TNF-α and IFN-γ can potentially serve as biological indicators of DLBCL tumor immune status, and combined application with the IPI score can be a robust prognostic indicator in patients with DLBCL.

摘要

本研究的目的是评估弥漫性大B细胞淋巴瘤(DLBCL)患者循环细胞因子的水平,并研究细胞因子水平、临床病理表现与患者预后之间的关联。2017年1月至2020年1月期间,该研究纳入了来自浙江省人民医院(中国杭州)的49例DLBCL患者、11例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤患者和67名健康对照者。采用流式细胞术检测血清白细胞介素(IL)-2、IL-4、IL-6、IL-10、IL-17、肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ水平。与健康对照者相比,DLBCL患者的IL-6、IL-10和IFN-γ水平显著升高(P<0.05)。循环乳酸脱氢酶水平升高的患者IL-10水平显著更高(P<0.05),而IL-6和IL-10水平升高均与C反应蛋白(CRP)水平升高相关,IL-6水平与血清CRP水平呈正相关(P<0.01;r=0.66)。此外,DLBCL患者的国际预后指数(IPI)风险分层与循环IL-6和IL-10水平密切相关。IL-6、IL-10和TNF-α水平升高与短期治疗效果较差相关(P<0.05)。此外,使用支持向量机算法获得的预测DLBCL患者短期治疗反应的模型准确性为81.63%。还发现,血清IL-6和IL-10水平升高以及IL-17水平降低与DLBCL患者生存<1年相关(P<0.05),尽管未发现细胞因子水平与长期总生存之间存在显著关联。总之,IL-6、IL-10、IL-17、TNF-α和IFN-γ的血清水平可能作为DLBCL肿瘤免疫状态的生物学指标,与IPI评分联合应用可作为DLBCL患者有力的预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8656/11005083/67a5fdf0b4c1/ol-27-05-14370-g00.jpg

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