State Key Laboratory of Systems Medicine for Cancer, Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Department of Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Cell Oncol (Dordr). 2024 Oct;47(5):1911-1925. doi: 10.1007/s13402-024-00974-2. Epub 2024 Aug 20.
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.
胃癌（GC）卵巢转移，通常称为克鲁肯贝格肿瘤，导致预后不良。然而，转移的原因尚不清楚。在这里，我们对两对对临床标本进行了整合的单细胞 RNA 测序（scRNA-Seq）分析，以研究胃癌卵巢转移的免疫微环境。
进行 scRNA-Seq 以确定胃癌卵巢转移中的免疫微环境。使用 CellChat 分析不同细胞类型之间的细胞间通讯。通过 clusterProfiler 中的 enrichKEGG 进行功能富集分析。使用 GEPIA2 评估某些基因和基因特征对预后的影响。
与原发性肿瘤相比，卵巢转移组织表现出异质性免疫微环境。在卵巢转移组织中观察到 T 和 B 细胞耗竭。与配对的相邻非肿瘤和原发性肿瘤相比，卵巢转移组织中的内皮细胞和成纤维细胞比例较高。与原发性卵巢癌相比，我们在 GC 的卵巢转移性组织中鉴定出具有 MFAP4 和 CAPNS1 表达的特定肿瘤相关成纤维细胞群。我们进一步定义了与转移相关的内皮细胞和与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不良。此外，与原发性肿瘤相比，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，并将促进发现胃癌卵巢转移的新治疗策略。
