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解析卵巢透明细胞癌的肿瘤微环境并阐明癌细胞的起源。

Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma.

作者信息

Kamaraj Uma S, Gautam Pradeep, Cheng Terence, Chin Tham Su, Tay Sun Kuie, Ho Tew Hong, Nadarajah Ravichandran, Goh Ronald Chin Hong, Wong Shing Lih, Mantoo Sangeeta, Busmanis Inny, Li Hu, Le Minh Tn, Li Qi-Jing, Lim Elaine Hsuen, Loh Yuin-Han

机构信息

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore.

Department of Obstetrics & Gynaecology, Singapore General Hospital, Outram Road, Singapore 169608.

出版信息

bioRxiv. 2024 Aug 8:2024.08.06.606821. doi: 10.1101/2024.08.06.606821.

Abstract

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC.

摘要

卵巢透明细胞癌(CCC)在东亚地区更为常见。它与子宫内膜异位症有关,子宫内膜异位症是一种良性疾病,在子宫外、腹膜表面、腹腔或盆腔空间发现子宫内膜(子宫内层)组织。与其他卵巢癌亚型相比,CCC对传统化疗的耐药性相对更强,且预后较差。在本研究中,我们招募了7例处于CCC四个阶段的患者并获取了他们的肿瘤组织。利用高分辨率单细胞RNA测序(scRNA-seq)对7例临床分期为1 - 4期的CCC患者的肿瘤及肿瘤微环境(TME)进行转录谱分析,以深入了解CCC的生物学机制。首先,我们构建了CCC肿瘤微环境(TME)的scRNA-seq资源。其次,我们确定了不同细胞类型的比例,并发现CCC中存在高水平的免疫浸润。第三,由于CCC与子宫内膜异位症有关,我们将CCC与两个公开可用的子宫内膜异位症scRNA-seq数据集进行了比较。CCC恶性细胞与在子宫内膜异位症中发现的腺分泌细胞和纤毛上皮细胞表现出相似性。最后,我们确定了CCC TME和子宫内膜异位症条件下各种细胞类型之间细胞间通讯的差异,以深入了解CCC中的转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f55f/11326226/6e5a1ddf5338/nihpp-2024.08.06.606821v1-f0001.jpg

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