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单细胞转录组学揭示了宫颈癌的细胞异质性和分子分层。

Single-cell transcriptomics reveals cellular heterogeneity and molecular stratification of cervical cancer.

机构信息

Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Commun Biol. 2022 Nov 10;5(1):1208. doi: 10.1038/s42003-022-04142-w.

Abstract

Cervical cancer (CC) is the most common gynecological malignancy, whose cellular heterogeneity has not been fully understood. Here, we performed single-cell RNA sequencing (scRNA-seq) to survey the transcriptomes of 57,669 cells derived from three CC tumors with paired normal adjacent non-tumor (NAT) samples. Single-cell transcriptomics analysis revealed extensive heterogeneity in malignant cells of human CCs, wherein epithelial subpopulation exhibited different genomic and transcriptomic signatures. We also identified cancer-associated fibroblasts (CAFs) that may promote tumor progression of CC, and further distinguished inflammatory CAF (iCAF) and myofibroblastic CAF (myCAF). CD8 T cell diversity revealed both proliferative (MKI67) and non-cycling exhausted (PDCD1) subpopulations at the end of the trajectory path. We used the epithelial signature genes derived from scRNA-seq to deconvolute bulk RNA-seq data of CC, identifying four different CC subtypes, namely hypoxia (S-H subtype), proliferation (S-P subtype), differentiation (S-D subtype), and immunoactive (S-I subtype) subtype. The S-H subtype showed the worst prognosis, while CC patients of the S-I subtype had the longest overall survival time. Our results lay the foundation for precision prognostic and therapeutic stratification of CC.

摘要

宫颈癌(CC)是最常见的妇科恶性肿瘤,其细胞异质性尚未完全阐明。在这里,我们进行了单细胞 RNA 测序(scRNA-seq),以调查来自三个 CC 肿瘤的 57669 个细胞的转录组,这些细胞均具有配对的正常邻近非肿瘤(NAT)样本。单细胞转录组学分析揭示了人类 CC 恶性细胞中广泛的异质性,其中上皮亚群表现出不同的基因组和转录组特征。我们还鉴定了可能促进 CC 肿瘤进展的癌相关成纤维细胞(CAF),并进一步区分了炎症性 CAF(iCAF)和肌成纤维性 CAF(myCAF)。CD8 T 细胞多样性在轨迹路径的末端揭示了增殖(MKI67)和非循环耗竭(PDCD1)亚群。我们使用 scRNA-seq 衍生的上皮特征基因对 CC 的批量 RNA-seq 数据进行去卷积,鉴定出四种不同的 CC 亚型,即缺氧(S-H 亚型)、增殖(S-P 亚型)、分化(S-D 亚型)和免疫活性(S-I 亚型)亚型。S-H 亚型预后最差,而 S-I 亚型的 CC 患者总生存时间最长。我们的研究结果为 CC 的精确预后和治疗分层奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a63/9649750/072fec4fe5ea/42003_2022_4142_Fig1_HTML.jpg

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