载脂蛋白E亚型对肝细胞癌患者免疫抑制及预后的影响
Effects of the subtypes of apolipoprotein E on immune inhibition and prognosis in patients with Hepatocellular Carcinoma.
发表日期:2024 Jul 08
作者:
Bowen Gao, Peiyun Zhou, Li Wang, Zhutao Wang, Yong Yi, Xian Li, Jian Zhou, Jia Fan, Shuangjian Qiu, Yang Xu
来源:
Epigenetics & Chromatin
摘要:
探讨髓源性抑制细胞(MDSC)的丰度和亚群以及载脂蛋白E(apoE)的亚型和表达是否影响肝细胞癌(HCC)患者的预后。 将31名HCC患者根据不同情况分为三组通过流式细胞术检测血液总apoE水平以检测免疫调节细胞的丰度。通过免疫荧光染色和免疫组化染色评估360例HCC患者肿瘤组织芯片中MDSC的丰度和亚群以及apoE2、apoE3、apoE4的表达。根据临床病理检查和10年随访数据,对360例患者进行单因素、多因素COX回归和Kaplan-Meier法进行生存分析。apoE较低组外周血中MDSC丰度较高HCC 患者的比例高于 apoE 较高组。 apoE 低水平组中单核细胞样 MDSC (M-MDSC) 的丰度高于高水平组 (p = 0.0399)。肿瘤组织中 apoE2 较低的 H 分数(HR = 6.140,p = 0.00005)和 apoE4 较高的 H 分数(HR = 7.001,p = 0.009)与较短的总生存期 (OS) 显着相关。肿瘤组织中多形核粒细胞样MDSCs(PMN-MDSCs,HR = 3.762,p = 0.000009)浸润较高和M-MDSCs占总细胞比例较小(HR = 0.454,p = 0.006)是肿瘤组织中较短的独立危险因素。无复发生存期(RFS)。HCC患者血浆中MDSC的丰度与apoE水平呈负相关。 HCC 组织中 apoE4 的表达表明预后不良,而 apoE2 可能是潜在的保护因素。© 2024。作者。
To investigate whether prognosis of patients with hepatocellular carcinoma (HCC) is affected by the abundance and subgroups of myeloid-derived suppressor cells (MDSCs) as well as subtypes and expression of apolipoprotein E (apoE).31 HCC patients were divided into three groups according to blood total apoE level for detecting the abundance of immunoregulatory cells by flow cytometry. Tumour tissue microarrays from 360 HCC patients were evaluated about the abundance and subgroups of MDSCs and the expression of apoE2, apoE3, apoE4 by immunofluorescence staining and immunohistochemistry staining. Survival analysis by means of univariate, multivariate COX regression and Kaplan-Meier methods of the 360 patients was performed based on clinical and pathological examinations along with 10 years' follow-up data.The lower apoE group presented higher abundance of MDSCs in the peripheral blood of HCC patients than higher apoE group. The abundance of monocyte-like MDSCs (M-MDSCs) was higher in the apoE low level group than high level group (p = 0.0399). Lower H-score of apoE2 (HR = 6.140, p = 0.00005) and higher H-score of apoE4 (HR = 7.001, p = 0.009) in tumour tissue were significantly associated with shorter overall survival (OS). The higher infiltration of polymorphonuclear granulocyte-like MDSCs (PMN-MDSCs, HR = 3.762, p = 0.000009) and smaller proportion of M-MDSCs of total cells (HR = 0.454, p = 0.006) in tumour tissue were independent risk factors for shorter recurrence-free survival (RFS).The abundance of MDSCs in HCC patients' plasma negatively correlates with the level of apoE. The expression of apoE4 in HCC tissue indicated a poor prognosis while apoE2 might be a potential protective factor.© 2024. The Author(s).