Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Clin Transl Med. 2021 Aug;11(8):e500. doi: 10.1002/ctm2.500.
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.
To address this question, we have performed a single-cell transcriptomics analysis of matched primary and metastatic HGSOC samples.
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.
This study uncovers new molecular features and the potential therapeutic target of HGSOC, which would advance the understanding and treatment of the disease.
高级别浆液性卵巢癌（HGSOC）是最常见且侵袭性最强的卵巢上皮癌组织学类型。该疾病的异质性和分子基础仍不完全清楚。
为了解决这个问题，我们对匹配的原发性和转移性 HGSOC 样本进行了单细胞转录组学分析。
总共对 13571 个细胞进行了分类，分为六种不同的细胞类型，包括上皮细胞、成纤维细胞、T 细胞、B 细胞、巨噬细胞和内皮细胞。鉴定出具有高增殖和耐药潜力的侵袭性上皮细胞亚群。进一步证实了几个在上皮细胞中高表达的新标志物在卵巢癌细胞生长和迁移中的作用。通过轨迹分析，与卵巢癌转移相关的多个信号通路（包括翻译机制）的失调。此外，单细胞调控网络推断和聚类（SCENIC）分析揭示了基因调控网络，并提出 JUN 信号通路可能是治疗卵巢癌的潜在靶点，这一点通过 JUN/AP-1 抑制剂 T-5224 得到了验证。最后，我们的研究描绘了上皮-成纤维细胞通讯图谱，并确定了卵巢癌发展过程中的几个重要的受体-配体复合物。
本研究揭示了 HGSOC 的新分子特征和潜在治疗靶点，将推进对该疾病的认识和治疗。
