ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1552841
This article is part of the Research TopicUnraveling GI Cancer Heterogeneity Through Single-Cell Multi-Omics ApproachesView all 4 articles
Single-cell RNA Profiling of Colorectal Granular-type Laterally Spreading Tumor Uncovers Progression Trajectory Toward Carcinoma and Transcriptional Signatures Favoring Lateral Morphogenesis
Provisionally accepted
- Peking University Third Hospital, Haidian, China
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Background. Colorectal laterally spreading tumors (LSTs) are defined as non-protruding neoplasms exceeding 10 mm in diameter that grow primarily along the intestinal wall. The morphogenetic mechanisms and evolutionary trajectories of granular-type LSTs (LST-Gs) towards colorectal carcinoma remain unclear. Methods. In this study, we investigate the transcriptional features of LST-Gs using single-cell RNA sequencing technology by comparing them with protruded-type adenomas (PAs) and normal mucosal tissues. Results. Adenomatous LST-Gs harbor an epithelial cell population with metaplastic differentiation, which are almost absent in PAs. Cells with a high degree of differentiation in LST-G demonstrate enhanced immunogenicity and robust adhesion/junction interactions. Furthermore, LST-Gs show upregulated expression of molecular chaperones and metallothioneins compared to PAs, reflecting a more hostile microenvironment similar to that observed in carcinoma stages. These characteristics suggest that LST-G exhibits greater heterogeneity compared to the earliest colorectal adenomas, mirroring the progression from precancerous states to cancer. Notably, the Arp2/3 complex is significantly upregulated in highly differentiated LST-G cell populations, potentially facilitating cell migration along the basement membrane, which highlights the similarities in cell motility between adenomatous LST-G and normal mucosal epithelium as well as serrated polyps (SERs). Conclusion. The differentiation state of cells within LST-G exhibits a close correlation with their diverse characteristics. Metaplastic differentiation, as a prominent feature at the transcriptional level, demonstrates significant associations with the genomic features, morphogenesis, and tumor progression of LST-G.
Keywords: Laterally spreading tumor (LST), adenomatous granular-type LST, Single-cell transcriptome, Metaplasia, Morphogenesis, colorectal precancerous lesion, Adenoma
Received: 29 Dec 2024; Accepted: 29 Aug 2025.
Copyright: © 2025 Gong, Zhang, Liu, Cui, Lu, LI, Gu, Zhang, Fu and Ding. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Zhang, Peking University Third Hospital, Haidian, China
Weiwei Fu, Peking University Third Hospital, Haidian, China
Shigang Ding, Peking University Third Hospital, Haidian, China
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