| Autor: |
Xin-Yang Liu, Yan-Bo Liu, Jia-Cheng Xu, Yi-Fei Zhang, Yuan-Yuan Ruan, Yi Zhao, Lin-Feng Wu, Jian-Wei Hu, Zhen Zhang, Meng-Jiang He, Tian-Yin Chen, Xiao-Yue Xu, Jing-Wei Zhang, Yi-Qun Zhang, Ping-Hong Zhou |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1608801/v1 |
| Popis: |
Background: The early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) is particularly important due to poor prognosis and the lack of effective therapies. This study aims to systematically describe the cellular atlas of human intramucosal ESCC.Methods: Five paired samples of intramucosal ESCC, para-ESCC esophageal tissue from endoscopically resected specimen, and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. A computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells.Results: A total of 164,715 cells were profiled. 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 and CXCR5 in PD1+CD4+ T cells and PADI4 in Mono2 cells were identified as new biomarkers for poor prognosis. Epithelial cells exhibited high intra-tumor heterogeneity and two evolutional trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normal differentiated epithelial cells or malignant cells, respectively. Intercellular interaction analysis based on ligand-receptor pairs revealed malignant cells interacting with CAFs via the MDK-NCL pathway, which is an important hallmark in the change of tumor microenvironment, and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumor invasion, and therefore suggesting a potential early biomarker of ESCC progression.Conclusions: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, providing unique insights into the development of novel biomarkers and potential intervention strategies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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