关键词: APOE Pancreatic cancer Prognosis TIL Treatment

Mesh : Aged Female Humans Male Middle Aged Apolipoproteins E / metabolism genetics Biomarkers, Tumor / metabolism blood Carcinoma, Pancreatic Ductal / immunology pathology metabolism blood Kaplan-Meier Estimate Lymphocytes, Tumor-Infiltrating / immunology metabolism Pancreatic Neoplasms / immunology pathology metabolism blood Prognosis Tumor Microenvironment / immunology

来  源:   DOI:10.1016/j.cyto.2024.156628

Abstract:
The expression level of apolipoprotein E (APOE) in pancreatic ductal adenocarcinoma (PDAC) and its effect on the prognosis of PDAC patients are not clear. The effect of APOE on the immune status of patients with PDAC has not been elucidated.
We obtained pancreatic cancer data from the TCGA and GETx databases. Patients with PDAC who underwent pancreatic surgery at the Second Affiliated Hospital of Jiaxing University between 2012 and 2021 were included. Clinical pathological data were recorded, plasma APOE levels were measured, and tissue samples were collected. A tissue microarray was generated using the collected tissue samples. APOE and CD4 staining was performed to determine immunoreactive scores (IRSs). The expression of APOE in the plasma and tumour tissues of pancreatic cancer patients was analysed and compared. The correlations between plasma APOE levels, tissue APOE levels and clinicopathological characteristics were analysed. Survival prognosis was analysed using Kaplan-Meier survival analysis and Cox multivariate regression analysis. The correlations between APOE expression levels and immune biomarkers and immune cells were further analysed. Single-cell analysis of APOE distribution in various cells was performed on the TISCH website.
APOE was highly expressed in the tumour tissue of pancreatic cancer patients, and high plasma APOE levels were associated with poor prognosis. Females, patients with high-grade disease and patients with pancreatic head carcinoma had high plasma APOE levels. High APOE expression in tumour tissues was associated with good prognosis. Mononuclear macrophages in the pancreatic cancer microenvironment primarily expressed APOE. APOE levels positively correlated with immune biomarkers, such as CD8A, PDCD1, GZMA, CXCL10, and CXCL9, in the tumour microenvironment. APOE promoted CD4 + T cell or dendritic cell infiltration in the tumour microenvironment.
APOE may affect the occurrence and development of pancreatic cancer by regulating the infiltration of immune cells in the tumour microenvironment.
摘要:
背景:载脂蛋白E(APOE)在胰腺导管腺癌(PDAC)中的表达水平及其对PDAC患者预后的影响尚不清楚。APOE对PDAC患者免疫状态的影响尚未阐明。
方法:我们从TCGA和GETx数据库获得了胰腺癌数据。纳入2012年至2021年在嘉兴大学附属第二医院接受胰腺手术的PDAC患者。记录临床病理资料,测量血浆APOE水平,并收集组织样本。使用收集的组织样品产生组织微阵列。进行APOE和CD4染色以确定免疫反应性评分(IRS)。分析并比较了APOE在胰腺癌患者血浆和肿瘤组织中的表达。血浆APOE水平之间的相关性,分析组织APOE水平和临床病理特征。采用Kaplan-Meier生存分析和Cox多因素回归分析进行生存预后分析。进一步分析APOE表达水平与免疫生物标志物和免疫细胞之间的相关性。在TISCH网站上进行各种细胞中APOE分布的单细胞分析。
结果:APOE在胰腺癌患者的肿瘤组织中高表达,高血浆APOE水平与不良预后相关。雌性,高级别疾病患者和胰头癌患者的血浆APOE水平较高。APOE在肿瘤组织中的高表达与良好的预后相关。胰腺癌微环境中的单核巨噬细胞主要表达APOE。APOE水平与免疫生物标志物呈正相关,例如CD8A,PDCD1,GZMA,肿瘤微环境中的CXCL10和CXCL9。APOE促进肿瘤微环境中的CD4+T细胞或树突状细胞浸润。
结论:APOE可能通过调节肿瘤微环境中免疫细胞的浸润而影响胰腺癌的发生发展。
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