The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma

Guozhong Jiang, Zhizhong Wang, Zhenguo Cheng, Weiwei Wang, Shuangshuang Lu, Zifang Zhang, Chinedu A. Anene, Faraz Khan, Yue Chen, Emma Bailey, Huisha Xu, Yunshu Dong, Peinan Chen, Zhongxian Zhang, Dongling Gao, Zhimin Wang, Jinxin Miao, Xia Xue, Pengju Wang, Lirong Zhang, Rathi Gangeswaran, Peng Liu, Louisa S. Chard Dunmall, Junkuo Li, Yongjun Guo, Jianzeng Dong, Nicholas R. Lemoine, Wencai Li (), Jun Wang () and Yaohe Wang ()
Additional contact information
Guozhong Jiang: The First Affiliated Hospital of Zhengzhou University
Zhizhong Wang: The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
Zhenguo Cheng: Zhengzhou University
Weiwei Wang: The First Affiliated Hospital of Zhengzhou University
Shuangshuang Lu: Zhengzhou University
Zifang Zhang: Zhengzhou University
Chinedu A. Anene: Queen Mary University of London
Faraz Khan: Queen Mary University of London
Yue Chen: Queen Mary University of London
Emma Bailey: Queen Mary University of London
Huisha Xu: Zhengzhou University
Yunshu Dong: Chinese Academy of Sciences
Peinan Chen: The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
Zhongxian Zhang: Zhengzhou University
Dongling Gao: The First Affiliated Hospital of Zhengzhou University
Zhimin Wang: Zhengzhou University
Jinxin Miao: Zhengzhou University
Xia Xue: Zhengzhou University
Pengju Wang: Zhengzhou University
Lirong Zhang: Zhengzhou University
Rathi Gangeswaran: Queen Mary University of London
Peng Liu: Queen Mary University of London
Louisa S. Chard Dunmall: Queen Mary University of London
Junkuo Li: Anyang Cancer Hospital
Yongjun Guo: The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
Jianzeng Dong: The First Affiliated Hospital of Zhengzhou University
Nicholas R. Lemoine: Zhengzhou University
Wencai Li: The First Affiliated Hospital of Zhengzhou University
Jun Wang: Queen Mary University of London
Yaohe Wang: Zhengzhou University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

Date: 2024
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DOI: 10.1038/s41467-024-53164-x

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