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整合单细胞RNA测序揭示了食管胃交界腺癌肝转移过程中的肿瘤异质性和微环境格局。

Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction.

作者信息

Xu Junrui, Sadiq Ussama, Zhao Wangruizhi, Xia Hengbo, Liu Yiwei, Zhang Renquan, Xu Aman

机构信息

Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.

Department of Thoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Front Immunol. 2025 Jan 9;15:1484234. doi: 10.3389/fimmu.2024.1484234. eCollection 2024.


DOI:10.3389/fimmu.2024.1484234
PMID:39850884
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11754270/
Abstract

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEGJ) is a highly aggressive tumor that frequently metastasizes to the liver. Understanding the cellular and molecular mechanisms that drive this process is essential for developing effective therapies. METHODS: We employed single-cell RNA sequencing to analyze the tumor heterogeneity and microenvironmental landscape in patients with AEGJ liver metastases. This approach enabled us to characterize the diverse cell populations involved in the liver metastatic process. RESULTS: Our analysis revealed a significant involvement of fibroblasts and mural cells in AEGJ liver metastasis. We identified a specific fibroblast type in AEGJ liver metastasis and observed distinct gene expression patterns between adenocarcinoma of the esophagogastric junction and other stomach adenocarcinomas. Our study demonstrated high expression of the SFRP2 gene in pericyte cells during the liver metastasis of AEGJ. The incorporation of GEO, TCGA, and immunofluorescence staining of SFRP2 expression enhanced our study. High expression of SFRP2 in pericytes may influence vascular stability and angiogenesis through the Wnt pathway. CONCLUSION: Our study provides novel insights into the cellular interactions and molecular mechanisms that underlie AEGJ liver metastasis. Targeting the identified subtype of fibroblasts or influencing SFRP2 gene expression in pericytes may offer new therapeutic strategies for combating this aggressive tumor.

摘要

背景:食管胃交界腺癌(AEGJ)是一种侵袭性很强的肿瘤,常转移至肝脏。了解驱动这一过程的细胞和分子机制对于开发有效的治疗方法至关重要。 方法:我们采用单细胞RNA测序来分析AEGJ肝转移患者的肿瘤异质性和微环境格局。这种方法使我们能够对参与肝转移过程的不同细胞群体进行特征描述。 结果:我们的分析显示,成纤维细胞和壁细胞在AEGJ肝转移中起重要作用。我们在AEGJ肝转移中鉴定出一种特定类型的成纤维细胞,并观察到食管胃交界腺癌与其他胃腺癌之间不同的基因表达模式。我们的研究表明,在AEGJ肝转移过程中,周细胞中SFRP2基因高表达。整合GEO、TCGA数据以及SFRP2表达的免疫荧光染色增强了我们的研究。周细胞中SFRP2的高表达可能通过Wnt途径影响血管稳定性和血管生成。 结论:我们的研究为AEGJ肝转移的细胞相互作用和分子机制提供了新的见解。靶向已鉴定的成纤维细胞亚型或影响周细胞中SFRP2基因的表达可能为对抗这种侵袭性肿瘤提供新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/f3896238cf10/fimmu-15-1484234-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/619d75288251/fimmu-15-1484234-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/58fdae26f75e/fimmu-15-1484234-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/c14fee5cbb34/fimmu-15-1484234-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/88a18bfe5bf9/fimmu-15-1484234-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/63035f05abb1/fimmu-15-1484234-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9828/11754270/f3896238cf10/fimmu-15-1484234-g011.jpg

相似文献

[1]
Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction.

Front Immunol. 2025-1-9

[2]
Characteristics of auto-quantified tumor-infiltrating lymphocytes and the prognostic value in adenocarcinoma of the esophagogastric junction, gastric adenocarcinoma, and esophageal squamous cell carcinoma.

Aging (Albany NY). 2024-7-5

[3]
Comparison of advanced adenocarcinomas of esophagogastric junction and distal stomach in Japanese patients.

Gastric Cancer. 2013-2-24

[4]
Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma.

BMC Cancer. 2011-10-20

[5]
Adenocarcinoma of the esophagogastric junction: characteristics of female patients and young adult patients based on a 12-year retrospective and prospective multicenter clinicoepidemiological cohort study in Japan.

BMC Gastroenterol. 2024-10-1

[6]
Tumor size predicts worse prognosis in esophagogastric junction adenocarcinoma.

Updates Surg. 2022-12

[7]
Immune Infiltration Subtypes Characterization and Identification of Prognosis-Related lncRNAs in Adenocarcinoma of the Esophagogastric Junction.

Front Immunol. 2021

[8]
Two distinct pathways of tumorigenesis of adenocarcinomas of the esophagogastric junction, related or unrelated to intestinal metaplasia.

Pathol Int. 2007-6

[9]
Study on the metastatic mechanism of LINC00115 in adenocarcinoma of the Esophagogastric junction.

Hum Mol Genet. 2025-3-7

[10]
Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China.

Int J Cancer. 2022-1-15

本文引用的文献

[1]
Revealing the association between East Asian oral microbiome and colorectal cancer through Mendelian randomization and multi-omics analysis.

Front Cell Infect Microbiol. 2024-9-17

[2]
Role of glycosylation-related gene MGAT1 in pancreatic ductal adenocarcinoma.

Front Immunol. 2024

[3]
Unravelling infiltrating T-cell heterogeneity in kidney renal clear cell carcinoma: Integrative single-cell and spatial transcriptomic profiling.

J Cell Mol Med. 2024-6

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Advancing immunotherapy for melanoma: the critical role of single-cell analysis in identifying predictive biomarkers.

Front Immunol. 2024

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Environ Toxicol. 2024-6

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Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma.

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IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells.

Br J Cancer. 2024-5

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