Single-Cell Transcriptomics Reveals Tissue Architecture in Ovarian Carcinosarcoma

Abstract

Background Ovarian carcinosarcoma (OCS) is one of rarest and most challenging histologic subtype of ovarian cancer. It features remarkable cellular heterogeneity. Using single-cell RNA sequencing, we characterize the cellular composition of the OCS and identify their molecular characteristics. Methods we applied single-cell RNA sequencing (scRNA-seq) to resected primary OCS for the in-depth analysis of tumor cells and the TME. Immunohistochemistry (IHC) staining was used for validation. Results Malignant epithelial and fibroblast cells displayed a high-degree of intratumoral heterogeneity. We revealed that certain epithelial cell subclusters had high levels of drug resistance scores and many active metabolic pathways. Furthermore, γδ T cells exhibited enriched IFNγ and IFNα response characteristics. Notably, we observed that macrophages were mainly M2-like macrophages with immunosuppressive properties. In addition, we found that the CD1A+/FCER1A+ DC cells were enriched with genes related to cytolytic effector pathway. Analyzing ligand-receptor interaction pairs between cell types, we identified broadly interacting cells and observed an interaction between the ANXA1+ epithelial population and FPR1+/FPR3+ myeloid cells. Conclusion Our findings provide a comprehensive single-cell transcriptomic landscape of human OCS and present a well-established resource for elucidating OCS diversity.