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单细胞转录组学揭示了原发性和转移性胃癌的多维度动态异质性。

Single-cell transcriptomics reveals the multidimensional dynamic heterogeneity from primary to metastatic gastric cancer.

作者信息

Zhang Yunpeng, Yang Kuan, Bai Jing, Chen Jing, Ou Qi, Zhou Wenzhe, Li Xia, Hu Congxue

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China.

出版信息

iScience. 2025 Jan 20;28(2):111843. doi: 10.1016/j.isci.2025.111843. eCollection 2025 Feb 21.

Abstract

Reprogramming of the tumor microenvironment (TME) plays a critical role in gastric cancer (GC) progression and metastasis. However, the multidimensional features between primary tumors and organ-specific metastases remain poorly understood. In this study, we characterized the dynamic heterogeneity of GC from primary to metastatic stages. We identified seven major cell types and 27 immune and stromal subsets. Immune cells decreased, while immunosuppressive cells increased in ovarian and peritoneal metastases. A 30-gene signature for ovarian metastasis was validated in GC cohorts. Additionally, critical ligand-receptor interactions, including in liver metastasis and in lymph node metastasis, were identified as potential therapeutic targets. Furthermore, , a transcription factor, was associated with poor prognosis and influenced immune cell interactions and migration. Collectively, this study provides valuable insights into TME dynamics in GC and highlights potential avenues for targeted therapies.

摘要

肿瘤微环境(TME)的重编程在胃癌(GC)的进展和转移中起着关键作用。然而,原发性肿瘤与器官特异性转移灶之间的多维度特征仍知之甚少。在本研究中,我们对GC从原发阶段到转移阶段的动态异质性进行了表征。我们鉴定出七种主要细胞类型以及27个免疫和基质亚群。在卵巢和腹膜转移灶中,免疫细胞减少,而免疫抑制细胞增加。一个用于卵巢转移的30基因特征在GC队列中得到验证。此外,关键的配体-受体相互作用,包括肝转移中的 和淋巴结转移中的 ,被确定为潜在的治疗靶点。此外,转录因子 与预后不良相关,并影响免疫细胞的相互作用和迁移。总体而言,本研究为GC中TME的动态变化提供了有价值的见解,并突出了靶向治疗的潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ced0/11834116/ee4d09f618ac/fx1.jpg

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