单细胞和 bulk RNA 测序相结合，揭示 NK 细胞标志物基因在胰腺导管腺癌中的预后和免疫状态。

Combining single-cell and bulk RNA sequencing, NK cell marker genes reveal a prognostic and immune status in pancreatic ductal adenocarcinoma.

机构信息

Research Institute of General Surgery, Jinling Hospital, Nanjing University Medical School, 305 Zhong Shan East Road, Nanjing, 210002, China.

Nanchang University, 461 Bayi Avenue, Nanchang, 330006, Jiangxi, China.

出版信息

Sci Rep. 2024 Jul 1;14(1):15037. doi: 10.1038/s41598-024-65917-1.

DOI:10.1038/s41598-024-65917-1

PMID:38951569

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11217423/

Abstract

The NK cell is an important component of the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC), also plays a significant role in PDAC development. This study aimed to explore the relationship between NK cell marker genes and prognosis, immune response of PDAC patients. By scRNA-seq data, we found the proportion of NK cells were significantly downregulated in PDAC and 373 NK cell marker genes were screened out. By TCGA database, we enrolled 7 NK cell marker genes to construct the signature for predicting prognosis in PDAC patients. Cox analysis identified the signature as an independent factor for pancreatic cancer. Subsequently, the predictive power of signature was validated by 6 GEO datasets and had an excellent evaluation. Our analysis of relationship between the signature and patients' immune status revealed that the signature has a strong correlation with immunocyte infiltration, inflammatory reaction, immune checkpoint inhibitors (ICIs) response. The NK cell marker genes are closely related to the prognosis and immune capacity of PDAC patients, and they have potential value as a therapeutic target.

摘要

NK 细胞是胰腺导管腺癌 (PDAC) 肿瘤微环境的重要组成部分，在 PDAC 发展中也起着重要作用。本研究旨在探讨 NK 细胞标记基因与 PDAC 患者预后、免疫反应的关系。通过 scRNA-seq 数据，我们发现 PDAC 中 NK 细胞的比例显著下调，并筛选出 373 个 NK 细胞标记基因。通过 TCGA 数据库，我们纳入 7 个 NK 细胞标记基因构建预测 PDAC 患者预后的signature。Cox 分析确定 signature 是胰腺癌的独立预后因素。随后，通过 6 个 GEO 数据集验证了 signature 的预测能力，评价结果良好。我们对 signature 与患者免疫状态之间的关系进行分析，结果表明 signature 与免疫细胞浸润、炎症反应、免疫检查点抑制剂 (ICIs) 反应具有很强的相关性。NK 细胞标记基因与 PDAC 患者的预后和免疫能力密切相关，具有作为治疗靶点的潜在价值。