Xu Junrui, Sadiq Ussama, Zhao Wangruizhi, Xia Hengbo, Liu Yiwei, Zhang Renquan, Xu Aman
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.
Front Immunol. 2025 Jan 9;15:1484234. doi: 10.3389/fimmu.2024.1484234. eCollection 2024.
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.
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。
Updates Surg. 2022-12
Front Cell Infect Microbiol. 2024-9-17
Front Cell Dev Biol. 2024-5-15