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

Jiang, G and Wang, Z and Cheng, Z and Wang, W and Lu, S and Zhang, Z and Anene, CA and Khan, F and Chen, Y and Bailey, E and Xu, H and Dong, Y and Chen, P and Zhang, Z and Gao, D and Wang, Z and Miao, J and Xue, X and Wang, P and Zhang, L and Gangeswaran, R and Liu, P and Chard Dunmall, LS and Li, J and Guo, Y and Dong, J and Lemoine, NR and Li, W and Wang, J and Wang, Y (2024) The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma. Nature Communications, 15. pp. 1-17. ISSN 2041-1723 DOI: https://doi.org/10.1038/s41467-024-53164-x

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.

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Divisions:	School of Health
Identification Number:	https://doi.org/10.1038/s41467-024-53164-x
Status:	Published
Refereed:	Yes
Publisher:	Springer Science and Business Media LLC
Additional Information:	© The Author(s) 2024
Uncontrolled Keywords:	Humans; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Female; Male; Prognosis; Middle Aged; Biomarkers, Tumor; Transcriptome; Mutation; Cell Line, Tumor; Gene Expression Profiling; Aged; E1A-Associated p300 Protein; Antigens, CD
SWORD Depositor:	Symplectic
Depositing User (symplectic)	Deposited by Mann, Elizabeth
Date Deposited:	24 Oct 2024 13:58
Last Modified:	24 Oct 2024 15:50
Item Type:	Article

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

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