Single-cell RNA transcriptomic analyses of tumor microenvironment of ovarian metastasis in gastric cancer.

IF 6.6 2区 医学 Q1 Medicine Cellular Oncology Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI:10.1007/s13402-024-00974-2
Guoyu Chen, Mingda Zhang, Xiaolin Lin, Qiqi Shi, Chenxin Xu, Bowen Sun, Xiuying Xiao, Haizhong Feng
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Abstract

Purpose: Ovarian metastasis of gastric cancer (GC), commonly referred to as Krukenberg tumors, leads to a poor prognosis. However, the cause of metastasis remains unknown. Here, we present an integrated single-cell RNA sequencing (scRNA-Seq) analysis of the immunological microenvironment of two paired clinical specimens with ovarian metastasis of GC.

Methods: scRNA-Seq was performed to determine the immunological microenvironment in ovarian metastasis of gastric cancer. CellChat was employed to analyze cell-cell communications across different cell types. Functional enrichment analysis was done by enrichKEGG in clusterProfiler. GEPIA2 was used to assess the influence of certain genes and gene signatures on prognosis.

Results: The ovarian metastasis tissues exhibit a heterogenous immunological microenvironment compared to the primary tumors. Exhaustion of T and B cells is observed in the ovarian metastasis tissues. Compared to the paired adjacent non-tumoral and primary tumors, the ratio of endothelial cells and fibroblasts is high in the ovarian metastasis tissues. Compared to primary ovarian cancers, we identify a specific group of tumor-associated fibroblasts with MFAP4 and CAPNS1 expression in the ovarian metastatic tissues of GC. We further define metastasis-related-endothelial and metastasis-related-fibroblast signatures and indicate that patients with these high signature scores have a poor prognosis. In addition, the ovarian metastasis tissue has a lower level of intercellular communications compared to the primary tumor.

Conclusion: Our findings reveal the immunological microenvironment of ovarian metastasis of gastric cancer and will promote the discovery of new therapeutic strategies for ovarian metastasis in gastric cancer.

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胃癌卵巢转移肿瘤微环境的单细胞 RNA 转录组分析
目的:胃癌(GC)的卵巢转移通常被称为克鲁肯伯格肿瘤,会导致不良预后。然而,转移的原因仍然不明。方法:采用单细胞RNA测序(scRNA-Seq)技术测定胃癌卵巢转移灶的免疫微环境。采用 CellChat 分析不同类型细胞间的细胞-细胞通讯。在 clusterProfiler 中使用 enrichKEGG 进行功能富集分析。GEPIA2 用于评估某些基因和基因特征对预后的影响:结果:与原发肿瘤相比,卵巢转移灶组织表现出异质性免疫微环境。结果:与原发肿瘤相比,卵巢转移灶组织表现出异质性免疫微环境。与相邻的非肿瘤和原发肿瘤相比,卵巢转移灶组织中内皮细胞和成纤维细胞的比例较高。与原发性卵巢癌相比,我们在 GC 的卵巢转移组织中发现了一组具有 MFAP4 和 CAPNS1 表达的特定肿瘤相关成纤维细胞。我们进一步定义了转移相关内皮细胞和转移相关成纤维细胞特征,并指出这些特征得分较高的患者预后较差。此外,与原发肿瘤相比,卵巢转移组织的细胞间通讯水平较低:我们的研究结果揭示了胃癌卵巢转移的免疫学微环境,将促进胃癌卵巢转移新治疗策略的发现。
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来源期刊
Cellular Oncology
Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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