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

Abstract

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.