胃癌卵巢转移肿瘤微环境的单细胞RNA转录组分析。
Single-cell RNA transcriptomic analyses of tumor microenvironment of ovarian metastasis in gastric cancer.
发表日期:2024 Aug 20
作者:
Guoyu Chen, Mingda Zhang, Xiaolin Lin, Qiqi Shi, Chenxin Xu, Bowen Sun, Xiuying Xiao, Haizhong Feng
来源:
Stem Cell Research & Therapy
摘要:
胃癌(GC)的卵巢转移,通常称为克鲁肯伯格肿瘤,导致预后不良。然而,转移的原因仍不清楚。在这里,我们对两对胃癌卵巢转移临床标本的免疫微环境进行了综合单细胞RNA测序(scRNA-Seq)分析。scRNA-Seq用于确定胃癌卵巢转移的免疫微环境。 CellChat 用于分析不同细胞类型之间的细胞间通信。功能富集分析由clusterProfiler中的enrichKEGG完成。 GEPIA2用于评估某些基因和基因特征对预后的影响。与原发肿瘤相比,卵巢转移组织表现出异质的免疫微环境。在卵巢转移组织中观察到 T 细胞和 B 细胞耗尽。与配对的相邻非肿瘤和原发肿瘤相比,卵巢转移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 卵巢转移组织中鉴定出一组具有 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的内皮细胞和转移相关的成纤维细胞特征,并表明具有这些高特征评分的患者预后较差。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微环境,并将促进胃癌卵巢转移新治疗策略的发现。© 2024施普林格自然瑞士股份公司。
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.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.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.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.© 2024. Springer Nature Switzerland AG.