Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis

Xiannian Zhang; Linna Peng; Yingying Luo; Shaosen Zhang; Yang Pu; Yamei Chen; Wenjia Guo; Jiacheng Yao; Mingming Shao; Wenyi Fan; Qionghua Cui; Yiyi Xi; Yanxia Sun; Xiangjie Niu; Xuan Zhao; Liping Chen; Yuqian Wang; Yachen Liu; Xinyu Yang; Chengcheng Wang; Ce Zhong; Wen Tan; Jianbin Wang; Chen Wu; Dongxin Lin

doi:10.1038/s41467-021-25539-x

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis

Nat Commun. 2021 Sep 6;12(1):5291. doi: 10.1038/s41467-021-25539-x.

Authors

Xiannian Zhang^#¹, Linna Peng^#², Yingying Luo^#², Shaosen Zhang^#², Yang Pu^#³, Yamei Chen^#², Wenjia Guo^{4

5}, Jiacheng Yao⁶, Mingming Shao², Wenyi Fan², Qionghua Cui², Yiyi Xi², Yanxia Sun², Xiangjie Niu², Xuan Zhao², Liping Chen², Yuqian Wang², Yachen Liu², Xinyu Yang², Chengcheng Wang², Ce Zhong², Wen Tan², Jianbin Wang⁷, Chen Wu^{8

9

10

11}, Dongxin Lin^{2

12

13

14}

Affiliations

¹ School of Basic Medical Sciences, Beijing Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
² Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Cancer Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China.
⁵ Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Regio, Urumqi, China.
⁶ School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
⁷ School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China. jianbinwang@tsinghua.edu.cn.
⁸ Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. chenwu@cicams.ac.cn.
⁹ Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. chenwu@cicams.ac.cn.
¹⁰ CAMS Oxford Institute (COI), Chinese Academy of Medical Sciences, Beijing, China. chenwu@cicams.ac.cn.
¹¹ CAMS key Laboratory of Cancer Genomic Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. chenwu@cicams.ac.cn.
¹² Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
¹³ CAMS key Laboratory of Cancer Genomic Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹⁴ Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China.

^# Contributed equally.

Abstract

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
B-Lymphocytes / immunology
B-Lymphocytes / pathology
Epithelial Cells / immunology
Epithelial Cells / pathology
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / immunology
Esophageal Neoplasms / mortality
Esophageal Neoplasms / pathology
Esophageal Squamous Cell Carcinoma / genetics*
Esophageal Squamous Cell Carcinoma / immunology
Esophageal Squamous Cell Carcinoma / mortality
Esophageal Squamous Cell Carcinoma / pathology
Female
Fibroblasts / immunology
Fibroblasts / pathology
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Myeloid Cells / immunology
Myeloid Cells / pathology
Neoplasm Proteins / classification
Neoplasm Proteins / genetics*
Neoplasm Proteins / immunology
Prognosis
Single-Cell Analysis
Stromal Cells / immunology*
Stromal Cells / pathology
Survival Analysis
T-Lymphocytes / immunology
T-Lymphocytes / pathology
Transcription, Genetic*
Tumor Microenvironment / genetics
Tumor Microenvironment / immunology
Whole Genome Sequencing

Substances

Neoplasm Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding