Zhou Bin, Liu Xiaolin, Hu Huanhuan, Li Zhipeng, Zhong Shanliang
Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China.
Office of Ethics Committee, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China.
Biochem Biophys Rep. 2025 Jul 18;43:102163. doi: 10.1016/j.bbrep.2025.102163. eCollection 2025 Sep.
We aimed to identify stromal cells associated with liver metastasis of gastric cancer (GC).
We downloaded single-cell RNA sequencing (scRNA-seq) datasets for GC tissues and adjacent normal tissues (NT), as well as liver metastases (LM) and healthy liver tissues (HL) from GEO. Additionally, we obtained RNA-Seq and clinical data from TCGA for the TCGA-STAD project. The datasets were analyzed using R software. Cell viability analysis were used to verify the potential drugs.
We obtained 7 GC, 2 NT, 5 LM and 3 HL datasets, as well as 448 RNA-Seq files. We identified 13 cell types from a total of 107,875 cells, which were further re-clustered into 38 subclusters. Our analyses showed that both GC and LM exhibited increased angiogenesis, cancer-associated fibroblasts (CAFs) were enriched in primary tumors, CD8 T cells in both GC and LM showed a declined proportion and increased necroptosis, NK cells were reduced in LM, and M2 macrophages (Mφ) exhibited high activities in both GC and LM. We found immune cells in HL and LM expressed more transcripts, suggesting the differences in tumor microenvironment (TME) between primary and metastatic tumors. Additionally, we identified 3 potential drugs that could be effective against both primary and metastatic tumors.
This study illustrated the heterogeneity of immune and stromal cells in TME of GC and LM, and identified several cell types associated with liver metastasis of GC. These cell types may serve as potential biomarkers or therapeutic targets in the future.
我们旨在鉴定与胃癌（GC）肝转移相关的基质细胞。
我们从基因表达综合数据库（GEO）下载了GC组织、邻近正常组织（NT）、肝转移灶（LM）及健康肝组织（HL）的单细胞RNA测序（scRNA-seq）数据集。此外，我们从癌症基因组图谱（TCGA）获取了针对TCGA-STAD项目的RNA测序和临床数据。使用R软件对数据集进行分析。采用细胞活力分析来验证潜在药物。
我们获得了7个GC、2个NT、5个LM和3个HL数据集，以及448个RNA测序文件。我们从总共107,875个细胞中鉴定出13种细胞类型，这些细胞进一步重新聚类为38个亚群。我们的分析表明，GC和LM均表现出血管生成增加，癌相关成纤维细胞（CAF）在原发性肿瘤中富集，GC和LM中的CD8 T细胞比例均下降且坏死性凋亡增加，LM中的自然杀伤（NK）细胞减少，M2巨噬细胞（Mφ）在GC和LM中均表现出高活性。我们发现HL和LM中的免疫细胞表达更多转录本，这表明原发性肿瘤和转移性肿瘤之间肿瘤微环境（TME）存在差异。此外，我们鉴定出3种可能对原发性和转移性肿瘤均有效的潜在药物。
本研究阐明了GC和LM的TME中免疫细胞和基质细胞的异质性，并鉴定出几种与GC肝转移相关的细胞类型。这些细胞类型未来可能作为潜在的生物标志物或治疗靶点。
