食管鳞状细胞癌中的CCR7：来自单细胞和批量转录组测序的鉴定

CCR7 in esophageal squamous cell carcinoma: an identification from single-cell and bulk transcriptome sequencing.

作者信息

Yu Yang, Zhao Qian, Cui Hongguang, Song Liang

机构信息

Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.

Nursing Department, Shandong Medical College, Jinan, 250000, China.

出版信息

Discov Oncol. 2025 Feb 14;16(1):183. doi: 10.1007/s12672-025-01927-3.

DOI:10.1007/s12672-025-01927-3

PMID:39953263

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11828771/

Abstract

BACKGROUND

Considering the involvement of CC-chemokine receptor type 7 (CCR7) in diverse tumors, the purpose of our current study is to reveal the specific mechanisms of CCR7 in esophageal squamous cell carcinoma (ESCC).

METHODS

We processed single-cell RNA sequencing data based on the Gene Expression Omnibus (GEO) database and utilizing Seurat software, and performed filtering and annotation to obtain different cell types. Genes related to gene ontology biological process and Hallmark were collected, and the enrichment of genes of interested in both single cell and TCGA-ESCA was quantified. Besides, genes related to CCR7 and KRAS signaling up were uploaded to construct the protein-protein interaction network. A series of cellular assays were incorporated to test the effects of CCR7 in ESCC cells.

RESULTS

28,281 cells were categorized into 4 non-immune cell classes (epithelial cells, smooth muscle cells, fibroblasts, endothelial cells) and 6 immune cell classes (mast cells, plasma B cells, B cells, neutrophils, macrophages, NK/T cells). CCR7 evidently expressed higher in epithelial cells of ESCA and was positively correlated with KRAS signaling up, inflammatory response and TNFA signaling via NFKB, with the most significant correlation witnessed between CCR7 and KRAS signaling up. Meanwhile, the positive correlation between KRAS signaling up and positive regulation of epithelial cell migration was observed. 12 common genes were related to both KRAS signaling up and positive regulation of epithelial cell migration, 3 of which (SOX9, FLT4 and HDAC9) were higher-expressed in M1 group of TCGA-ESCA. Besides, CCR7 as well as its ligands CCL19 and CCL21 was shown to express higher in ESCC cells, where increased level of immune response-related cytokines was seen. CCR7 knockdown diminished migration and proliferation as well as Macrophage M2 polarization.

CONCLUSION

CCR7 was highly-expressed in ESCC and positively correlated with KRAS signaling up, which may contribute to the migration of ESCC cells.

摘要

背景

鉴于CC趋化因子受体7（CCR7）参与多种肿瘤，我们当前研究的目的是揭示CCR7在食管鳞状细胞癌（ESCC）中的具体机制。

方法

我们基于基因表达综合数据库（GEO）处理单细胞RNA测序数据，并利用Seurat软件进行过滤和注释以获得不同细胞类型。收集与基因本体生物学过程和特征相关的基因，并对单细胞和TCGA-ESCA中感兴趣基因的富集情况进行量化。此外，上传与CCR7和KRAS信号上调相关的基因以构建蛋白质-蛋白质相互作用网络。纳入一系列细胞实验以测试CCR7对ESCC细胞的影响。

结果

28281个细胞被分为4种非免疫细胞类别（上皮细胞、平滑肌细胞、成纤维细胞、内皮细胞）和6种免疫细胞类别（肥大细胞、浆B细胞、B细胞、中性粒细胞、巨噬细胞、NK/T细胞）。CCR7在ESCA的上皮细胞中明显高表达，且与KRAS信号上调、炎症反应和通过NFKB的TNFA信号呈正相关，其中CCR7与KRAS信号上调之间的相关性最为显著。同时，观察到KRAS信号上调与上皮细胞迁移的正调控之间存在正相关。有12个共同基因与KRAS信号上调和上皮细胞迁移的正调控均相关，其中3个（SOX9、FLT4和HDAC9）在TCGA-ESCA的M1组中高表达。此外，CCR7及其配体CCL19和CCL21在ESCC细胞中表达较高，其中免疫反应相关细胞因子水平升高。CCR7敲低减少了迁移、增殖以及巨噬细胞M2极化。