Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma  

作　　者：Junfen XU Mengyan TU 

机构地区：[1]Department of Gynecologic Oncology,Women’s Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China [2]Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology,Hangzhou 310006,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第8期686-699,共14页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(No.82072855);the Fundamental Research Funds for the Central Universities of China(No.2023QZJH54).

摘　　要：Objective:The present study used single-cell RNA sequencing(scRNA-seq)to characterize the cellular composition of ovarian carcinosarcoma(OCS)and identify its molecular characteristics.Methods:scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment.Immunohistochemistry staining was used for validation.The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma(HGSOC)tumors and other OCS tumors.Results:Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study.We identified four epithelial cell subclusters with different biological roles.Among them,epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog(BRCA1)and DNA topoisomerase 2-α(TOP2A)expression and was related to drug resistance and cell cycle.We analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor(FGF)and pleiotrophin(PTN)signalings were the main pathways contributing to communication between these cells.Moreover,we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS data.All the epithelial subclusters in the OCS tumor could be found in the HGSOC samples.Notably,the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor,characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1(CYP24A1),collagen type XXIIIα1 chain(COL23A1),cholecystokinin(CCK),bone morphogenetic protein 7(BMP7),PTN,Wnt inhibitory factor 1(WIF1),and insulin-like growth factor 2(IGF2).Moreover,this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian tissue.Conclusions:This study provides the single-cell transcriptomics signature of human OCS,which constitutes a new resource for elucidating OCS diversity.

关 键 词：Ovarian carcinosarcoma Single-cell RNA sequencing(scRNA-seq) Tumor heterogeneity 

分 类 号：R737.31[医药卫生—肿瘤]