Department of Liver Surgery and Transplantation, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Liver Cancer Institute, Fudan University, Shanghai, 200032, China.
Shanghai Cancer Centre, Fudan University, Shanghai, 200032, China.
J Cancer Res Clin Oncol. 2024 Jul 8;150(7):341. doi: 10.1007/s00432-024-05856-6.
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.
研究肝癌（HCC）患者的预后是否受髓系来源抑制细胞（MDSC）丰度及其亚群以及载脂蛋白 E（apoE）的亚型和表达的影响。
根据血液总 apoE 水平将 31 例 HCC 患者分为三组，通过流式细胞术检测免疫调节细胞的丰度。通过免疫荧光染色和免疫组织化学染色对 360 例 HCC 患者的肿瘤组织微阵列进行 MDSC 丰度和亚群以及 apoE2、apoE3、apoE4 的表达评估。对 360 例患者进行单因素、多因素 COX 回归和 Kaplan-Meier 生存分析，根据临床和病理检查以及 10 年随访数据进行。
apoE 较低组 HCC 患者外周血 MDSC 丰度高于 apoE 较高组。apoE 低水平组单核细胞样 MDSC（M-MDSC）丰度高于高水平组（p=0.0399）。肿瘤组织中 apoE2 的 H 评分较低（HR=6.140，p=0.00005）和 apoE4 的 H 评分较高（HR=7.001，p=0.009）与总生存期（OS）较短显著相关。肿瘤组织中多形核粒细胞样 MDSC（PMN-MDSC，HR=3.762，p=0.000009）浸润较高和总细胞中 M-MDSC 的比例较小（HR=0.454，p=0.006）是复发无进展生存期（RFS）较短的独立危险因素。
HCC 患者血浆中 MDSC 的丰度与 apoE 的水平呈负相关。HCC 组织中 apoE4 的表达提示预后不良，而 apoE2 可能是潜在的保护因素。
