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早期胰腺导管腺癌中 LILR 家族基因表达与肿瘤浸润免疫细胞的综合分析。

Comprehensive analysis of LILR family genes expression and tumour-infiltrating immune cells in early-stage pancreatic ductal adenocarcinoma.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, China.

出版信息

IET Syst Biol. 2023 Apr;17(2):39-57. doi: 10.1049/syb2.12058. Epub 2023 Feb 7.

DOI:10.1049/syb2.12058
PMID:36748687
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10116025/
Abstract

Leucocyte immunoglobulin-like receptors (LILRs) are closely related to tumourigenesis, but their clinical value in early-stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy remains unknown. Kaplan-Meier and Cox proportional hazards regression models is used to investigate the association between LILR expression and prognosis in tumour biopsies and peripheral blood mononuclear cells. Risk score was calculated for each patient based on the prognostic model. DAVID, STRING, GeneMANIA, and GSEA were used to conduct pathway and functional analyses. The CIBERSORT algorithm is used to analyse tumour-infiltrating immune cells. Survival analysis showed that high levels of LILRA4 (p = 0.006) and LILRB4 (p = 0.04) were significantly associated with better overall survival. High levels of LILRA2 (p = 0.008) and LILRB4 (p = 0.038) were significantly associated with better relapse-free survival. JAK-STAT signalling pathway, regulation of T cell activation, regulation of the immune effector process, and tumour necrosis factor superfamily cytokine production were involved in molecular mechanisms that affected poor prognoses in the high-risk group in GSEA. CIBERSORT demonstrated that the high-risk group had significantly higher infiltrating fraction of memory-activated CD4 T cells and activated NK cells and lower fraction of resting dendritic cells and neutrophils. LILRB4 plays crucial roles in affecting the clinical outcomes of early-stage PDAC.

摘要

白细胞免疫球蛋白样受体 (LILRs) 与肿瘤发生密切相关，但它们在胰十二指肠切除术后早期胰腺导管腺癌 (PDAC) 中的临床价值尚不清楚。使用 Kaplan-Meier 和 Cox 比例风险回归模型来研究肿瘤活检和外周血单核细胞中 LILR 表达与预后之间的关系。根据预后模型为每位患者计算风险评分。使用 DAVID、STRING、GeneMANIA 和 GSEA 进行途径和功能分析。使用 CIBERSORT 算法分析肿瘤浸润免疫细胞。生存分析表明，LILRA4 水平高 (p = 0.006) 和 LILRB4 水平高 (p = 0.04) 与总生存期延长显著相关。LILRA2 水平高 (p = 0.008) 和 LILRB4 水平高 (p = 0.038) 与无复发生存期延长显著相关。JAK-STAT 信号通路、T 细胞激活调节、免疫效应子过程调节和肿瘤坏死因子超家族细胞因子产生参与了 GSEA 中影响高危组不良预后的分子机制。CIBERSORT 表明，高危组记忆激活的 CD4 T 细胞和活化的 NK 细胞浸润分数显著更高，而静止树突状细胞和中性粒细胞浸润分数显著更低。LILRB4 在影响早期 PDAC 的临床结局方面发挥着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/10116025/6edd70764942/SYB2-17-39-g006.jpg
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