Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma

Junfen XU; Mengyan TU

doi:10.1631/jzus.B2300407

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Research Article | Updated：2024-08-19

Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma
Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma
单细胞转录组学揭示卵巢癌肉瘤的肿瘤特征
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 8, Pages: 686-699(2024)
Affiliations：

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
Funds：
DOI：10.1631/jzus.B2300407
CLC：
CSTR：
Published： 15 August 2024 ，

Received： 12 June 2023 ，

Revised： 21 September 2023 ，
Accepted：

许君芬,屠梦雁.单细胞转录组学揭示卵巢癌肉瘤的肿瘤特征[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(08):686-699.

Junfen XU, Mengyan TU. Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(8):686-699(2024)
许君芬,屠梦雁.单细胞转录组学揭示卵巢癌肉瘤的肿瘤特征[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(08):686-699. DOI： 10.1631/jzus.B2300407.

Junfen XU, Mengyan TU. Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(8):686-699(2024) DOI： 10.1631/jzus.B2300407.

摘要

本研究旨在通过使用单细胞RNA测序（scRNA-seq）来表征卵巢癌肉瘤的细胞组成并鉴定其分子特征。我们将scRNA-seq应用于手术切除的原发性卵巢癌肉瘤标本，对肿瘤细胞和肿瘤微环境进行分析，同时采用免疫组织化学染色进行验证，最后将卵巢癌肉瘤的scRNA-seq数据与高级别浆液性卵巢癌肿瘤及其他研究中的卵巢癌肉瘤数据进行比较。结果显示，在该卵巢癌肉瘤患者中可同时检测到恶性上皮细胞和恶性间充质细胞。我们鉴定了四个具有不同生物学作用的上皮细胞亚簇，其中上皮细胞亚簇4表现出高水平的乳腺癌1号基因（BRCA1）和DNA拓扑异构酶II α（TOP2A）表达

，这与耐药性和细胞周期有关。通过对上皮细胞和间充质细胞之间的相互作用分析，我们还发现成纤维细胞生长因子（FGF）和多功能生长因子（PTN）信号通路是促进这种细胞通讯的主要途径。此外，通过将这种卵巢癌肉瘤的恶性上皮和间充质细胞与课题组前期发表的高级别浆液性卵巢癌scRNA-seq数据及其他已发表的卵巢癌肉瘤数据进行对比，我们发现在高级别浆液性卵巢癌样本中存在该卵巢癌肉瘤中的所有上皮亚簇。值得注意的是，间充质亚簇C14在卵巢癌肉瘤中表现出特异性表达模式，其特征是肽基丙基异构酶24A1（

CYP24A1

）、胶原XXIII型α1链（

COL23A1

）、胆囊收缩素（

CCK

）、骨形态发生蛋白7（

BMP7

）、

PTN

、Wnt抑制因子1（

WIF1

）和胰岛素样生长因子2（

IGF2

）表达水平的升高；当与另一份已发表的卵巢癌肉瘤数据及正常卵巢组织相比，该亚簇则表现出截然不同的特征。综上，本研究提供了人类卵巢癌肉瘤的单细胞转录组特征，并为阐明卵巢癌肉瘤多样性提供了新的资源。

Abstract

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 a

nd 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 XXIII α1 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

卵巢癌肉瘤单细胞RNA测序肿瘤异质性

Keywords

Ovarian carcinosarcomaSingle-cell RNA sequencing (scRNA-seq)Tumor heterogeneity

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