研究动态
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单细胞转录组学揭示了卵巢癌肉瘤的肿瘤景观。

Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma.

发表日期:2024 Aug 15
作者: Junfen Xu, Mengyan Tu
来源: Journal of Zhejiang University-SCIENCE B

摘要:

本研究利用单细胞RNA测序(scRNA-seq)来表征卵巢癌肉瘤(OCS)的细胞组成并鉴定其分子特征。scRNA-seq在切除的原发性OCS中进行,以深入分析肿瘤细胞和肿瘤微环境。使用免疫组织化学染色进行验证。将OCS的scRNA-seq数据与高级别浆液性卵巢癌(HGSOC)肿瘤和其他OCS肿瘤的scRNA-seq数据进行比较。在本研究的OCS患者中观察到恶性上皮细胞和恶性间质细胞。我们确定了四个具有不同生物学作用的上皮细胞亚群。其中,上皮亚簇4呈现高水平的乳腺癌1型易感蛋白同源物(BRCA1)和DNA拓扑异构酶2-α(TOP2A)表达,并且与耐药性和细胞周期相关。我们分析了上皮细胞和间充质细胞之间的相互作用,发现成纤维细胞生长因子(FGF)和多效素(PTN)信号传导是促进这些细胞之间通讯的主要途径。此外,我们将该 OCS 肿瘤的恶性上皮细胞和间质细胞与我们之前发表的 HGSOC scRNA-seq 数据和 OCS 数据进行了比较。 OCS 肿瘤中的所有上皮亚簇都可以在 HGSOC 样本中找到。值得注意的是,间充质亚簇 C14 在 OCS 肿瘤中表现出特异性表达模式,其特征是细胞色素 P450 家族 24 亚家族 A 成员 1 (CYP24A1)、胶原蛋白 XXIII 型 α1 链 (COL23A1)、胆囊收缩素 (CCK)、骨形态发生蛋白 7 的表达升高(BMP7)、PTN、Wnt 抑制因子 1 (WIF1) 和胰岛素样生长因子 2 (IGF2)。此外,与先前发表的另一种 OCS 肿瘤和正常卵巢组织相比,该亚群表现出独特的特征。这项研究提供了人类 OCS 的单细胞转录组学特征,这为阐明 OCS 多样性提供了新的资源。
The present study used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of ovarian carcinosarcoma (OCS) and identify its molecular characteristics.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.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 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.This study provides the single-cell transcriptomics signature of human OCS, which constitutes a new resource for elucidating OCS diversity.