Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.
Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.
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DOI：
10.1002/ctm2.1203
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发表时间：
2023-03
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
由于缺乏有效的治疗方法和预后不良，对食管鳞癌的早期诊断和干预尤为重要。由于需要从ESD获得新鲜和高质量的标本，因此在单细胞水平上对早期ESCC进行全面研究的情况很少。本研究旨在系统地描述人粘膜内鳞状细胞癌的细胞图谱。采用5对粘膜内食管鳞癌、癌旁食管镜下切除的食道组织和外周血单个核细胞进行单链RNA序列分析。应用计算流水线单细胞代谢技术对单细胞的代谢多样性进行量化。总共分析了164个715个细胞。在食管鳞癌的发生过程中，上皮细胞表现出高度的异质性和两种不同的进化轨迹，从增殖的细胞开始，然后通过中间状态，分别到达正常分化的上皮细胞或恶性细胞的两种不同的终末状态。CD8+TES、Tregs和PD1+CD4+T细胞的丰富，提示机体处于疲惫和抑制的免疫微环境。免疫细胞中的几个基因，如CXCL13、CXCR5和PADI4，被认为是预后不良的新生物标志物。与进展性ESCC相比，与转移和血管生成相关的新的恶性细胞亚群也被识别出来。基于配体-受体对的细胞间相互作用分析表明，恶性细胞亚群通过MDK-NCL途径与CAF相互作用，细胞增殖实验和IHC证实了这一点。这表明这种相互作用可能是肿瘤微环境早期改变的一个重要标志，并可作为激活CAF以刺激促进肿瘤侵袭的下游通路的标志。这项研究揭示了人粘膜内ESCC细胞亚群和转录水平的变化，这可能为开发新的生物标志物和潜在的干预策略提供独特的见解。
The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single‐cell level is rare due to the need for fresh and high‐quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. Five paired samples of intramucosal ESCC, para‐ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA‐seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. A total of 164 715 cells were profiled. Epithelial cells exhibited high intra‐tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEXs, Tregs and PD1+CD4+T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand–receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK–NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.
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影响因子：
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作者：
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DOI：
10.1007/s10388-018-0641-9
发表时间：
2019-01
期刊：
Esophagus : official journal of the Japan Esophageal Society
影响因子：
--
作者：
Kitagawa Y;Uno T;Oyama T;Kato K;Kato H;Kawakubo H;Kawamura O;Kusano M;Kuwano H;Takeuchi H;Toh Y;Doki Y;Naomoto Y;Nemoto K;Booka E;Matsubara H;Miyazaki T;Muto M;Yanagisawa A;Yoshida M
通讯作者：
Yoshida M
影响因子：
6.2
作者：
Chen Z;Huang Y;Hu Z;Zhao M;Bian Y;Chen Z;Zheng Y;Bi G;Pang Y;Zhan C;Lin Z;Guo W;Wang Q;Tan L
通讯作者：
Tan L
影响因子：
11.2
作者：
Kanao, H;Enomoto, T;Murata, Y
通讯作者：
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