2. Academic Validation
  3. Single-cell transcriptomes reveal heterogeneity of high-grade serous ovarian carcinoma

Single-cell transcriptomes reveal heterogeneity of high-grade serous ovarian carcinoma

  • Clin Transl Med. 2021 Aug;11(8):e500. doi: 10.1002/ctm2.500.
Qian Hao 1 2,  Jiajia Li 3 2,  Qinghua Zhang 1 2,  Fei Xu 3 2,  Bangxiang Xie 4,  Hua Lu 5,  Xiaohua Wu 3 2,  Xiang Zhou 1 2 6 7
Affiliations

Affiliations

  • 1 Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 3 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
  • 4 Beijing YouAn Hospital, Capital Medical University, Beijing Institute of Hepatology, Beijing, China.
  • 5 Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana.
  • 6 Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
  • 7 Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
PMID: 34459128 DOI: 10.1002/ctm2.500
Abstract

Background: High-grade serous ovarian carcinoma (HGSOC) is the most common and aggressive histotype of epithelial ovarian Cancer. The heterogeneity and molecular basis of this disease remain incompletely understood.

Methods: To address this question, we have performed a single-cell transcriptomics analysis of matched primary and metastatic HGSOC samples.

Results: A total of 13 571 cells are categorized into six distinct cell types, including epithelial cells, fibroblast cells, T cells, B cells, macrophages, and endothelial cells. A subset of aggressive epithelial cells with hyperproliferative and drug-resistant potentials is identified. Several new markers that are highly expressed in epithelial cells are characterized, and their roles in ovarian Cancer cell growth and migration are further confirmed. Dysregulation of multiple signaling pathways, including the translational machinery, is associated with ovarian Cancer metastasis through the trajectory analysis. Moreover, single-cell regulatory network inference and clustering (SCENIC) analysis reveals the gene regulatory networks and suggests the JUN signaling pathway as a potential therapeutic target for treatment of ovarian Cancer, which is validated using the JUN/AP-1 Inhibitor T-5224. Finally, our study depicts the epithelial-fibroblast cell communication atlas and identifies several important receptor-ligand complexes in ovarian Cancer development.

Conclusions: This study uncovers new molecular features and the potential therapeutic target of HGSOC, which would advance the understanding and treatment of the disease.

Keywords

chemoresistance; gene regulatory network; intercellular communication; metastasis; single-cell RNA-seq.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12270
    99.59%, c-Fos/AP-1 Inhibitor