Integrative single-cell transcriptomic analysis deciphers heterogeneous characteristics of gastrointestinal tract cancer

Sep 23, 2026

Gastrointestinal tract cancer (GIC), including oesophageal, gastric, and colorectal cancer, is marked by high incidence and mortality and shares tumourigenic processes, yet its common and heterogeneous molecular patterns at single-cell resolution remain insufficiently defined. This study integrates single-cell RNA-seq from over one million annotated cells across 577 specimens to uncover epithelial meta-programs, non-epithelial subtypes, tumour microenvironment interactions, and metaplastic signatures. Results reveal 24 consensus epithelial meta-programs and 42 non-epithelial subtypes, with distinct immune and metaplastic phenotypes across cancer types.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Background

Methods

Results

Epithelial meta-programs and non-epithelial subtypes

Cancer-type-specific immune and stress features

Metaplastic signatures and similarity to colorectal cancer

DOI: 10.1002/ctm2.70415 RESEARCH ARTICLE Integrative single-cell transcriptomic analysis deciphers heterogeneous characteristics of gastrointestinal tract cancer Chuwen Sun1,2 Tong Li2, 3,4 Xin Jin1, 5 Zhihui Xiu4 Hang Su4 Huanming Yang1,2 Ming Liu6 Kui Wu1,2, 3,4, 5 1 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China 2 HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou, China 3Jiangxi Provincial Key Laboratory of Organ Development and Epigenetics, School of Basic Medicine, Jinggangshan University, Ji’an, China 4 BGI Genomics, Harbin, Heilongjiang, China 5 Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China 6 Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China Correspondence Ming Liu, Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150000, China. [Email:](Email: mingliu35@hrbmu.edu.cn)[ mingliu35@hrbmu.edu.cn](Email: mingliu35@hrbmu.edu.cn) Kui Wu, College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. [Email:](Email: wukui@genomics.cn)[ wukui@genomics.cn](Email: wukui@genomics.cn) Graphical Abstract 1. Twenty-four meta-programs and forty-two non-epithelial cells subtypes were identified in gastrointestinal tract cancer using over one million cells. 2. Esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) display unique epithelial characteristics influenced by specialized tumor microenvironment. 3. GC and EC with a metaplastic phenotype demonstrate overlapping features with CRC. Clin. Transl. Med. 2025;15:e70415 . [https://doi.org/10.1002/ctm2.70415](https://doi.org/10.1002/ctm2.70415) [wileyonlinelibrary.com/journal/ctm2](wileyonlinelibrary.com/journal/ctm2) DOI: 10.1002/ctm2.70415 RESEARCH ARTICLE Integrative single-cell transcriptomic analysis deciphers heterogeneous characteristics of gastrointestinal tract cancer Chuwen Sun1,2 Tong Li2, 3,4 Xin Jin1, 5 Zhihui Xiu4 Hang Su4 Huanming Yang1,2 Ming Liu6 Kui Wu1,2, 3,4, 5 1 College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China 2 HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), BGI Research, Hangzhou, China 3Jiangxi Provincial Key Laboratory of Organ Development and Epigenetics, School of Basic Medicine, Jinggangshan University, Ji’an, China 4 BGI Genomics, Harbin, Heilongjiang, China 5 Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen, China 6 Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China Correspondence Ming Liu, Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150000, China. [Email:](Email: mingliu35@hrbmu.edu.cn)[ mingliu35@hrbmu.edu.cn](Email: mingliu35@hrbmu.edu.cn) Kui Wu, College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. [Email:](Email: wukui@genomics.cn)[ wukui@genomics.cn](Email: wukui@genomics.cn) Funding information Zhejiang Science and Technology Department, Grant/Award Number: 2023C03103; National Natural Science Foundation of China, Grant/Award Number: 32370978; Heilongjiang Provincial Key R&D Program, Grant/Award Number: 2023ZX07D05; Natural Science Foundation of Heilongjiang Province, Grant/Award Number: ZL2024H011 Abstract Background: Gastrointestinal tract cancer (GIC), including oesophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC), is characterised with high global incidence and mortality rates, with similar tumourigenic processes. However, the common and heterog

FAQs

What is the main research goal of the study?

To integrate large-scale single-cell transcriptomic data to systematically decipher heterogeneous molecular characteristics of gastrointestinal tract cancer, including common and subtype-specific features.

How were epithelial meta-programs and non-epithelial subtypes identified?

Non-negative matrix factorisation (NMF) was used to identify epithelial cell meta-programs, and distinct subtypes were resolved for non-epithelial cells.

What did the study find regarding differences between oesophageal, gastric, and colorectal cancers?

The study reports oesophageal cancer shows unique stress-related program activity and an exhausted tumour microenvironment, while gastric cancer shows EMT-related signatures and an activated immune phenotype. Metaplastic phenotypes in gastric and oesophageal cancers overlap with colorectal cancer features.

Sep 23, 2026

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