Dataset Information

Single-cell RNA profiling of colorectal granular-type laterally spreading tumor uncovers progression trajectory toward carcinoma and transcriptional signatures favoring lateral morphogenesis.

ABSTRACT:

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.

SUBMITTER: Gong Y

PROVIDER: S-EPMC12463592 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Single-cell RNA profiling of colorectal granular-type laterally spreading tumor uncovers progression trajectory toward carcinoma and transcriptional signatures favoring lateral morphogenesis.

Gong Yueqing Y Zhang Yuxin Y Liu Xun X Cui Rongli R Lu Jingjing J Li Jun J Gu Fang F Zhang Jing J Ding Shigang S Fu Weiwei W

Frontiers in oncology 20250912

<h4>Background</h4>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.<h4>Methods</h4>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 n ...[more]

PMID: 41018078

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Project description:Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide, with 1.65 million new cases and almost 835,000 deaths in 2015. CRC is still a major cause of mortality associated with cancer, although the wide spread of the screening program has led to a reduction in the mortality rate compared to the last decades. CRCs derive from precancerous lesions that may be polypoid or non-polypoid according to the Paris classification. Thus, resection in an early stage could led to a CRC mortality reduction. Laterally spreading tumors (LST) are non-polypoid lesions of at least 1 cm in diameter that have lateral growth rather than upward or downward growth. The prevalence of LSTs ranges from 1 to 6% of all colorectal lesions. LSTs can be divided into two groups: granular LSTs, which include homogeneous and granular mixed forms and non-granular (NG) LSTs, which include pseudo-depressed and flat-elevated forms. Histologically, 90% of LSTs are adenomas and having a low incidence of invasive neoplasia, these lesions can be removed endoscopically. However, as evidenced by a recent meta-analysis published by Bogie Roel MM et al on Endoscopy, the type of LST and the distal or proximal colonic localization could represent predictors of submucosal invasion and could simplify the therapeutic decision for the removal of these lesions. GM-LSTs and pseudo-depressed NG-LSTs predominantly localize in the distal portion of the colon and have a submucosal invasion rate of 10,5% and 31,6% respectively. LSTs can be removed both through endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). The main limitation of EMR is that large lesions require a piecemeal approach, resulting in a non-optimal histological evaluation and a high risk of recurrence. ESD instead allows a higher rate of en bloc resections, thus resulting more curative and reducing the risk of having partial and incomplete resections, which can lead to disease recurrence/non curative resection. LST-GM are characterized by the presence of a granular appearance with a main nodule and represent approximately 1/4 of the LSTs. There are no guidelines indicating the proper resective technique of these lesions. The European Society of Gastrointestinal Endoscopy (ESGE) suggests to consider ESD for the removal of colorectal lesions that are > 20 mm in size, with a depressed and irregular morphology or a non-granular surface pattern, as these lesions have a high probability of having a limited submucosal invasion. Moreover ESD can be used to treat lesions that cannot be completely removed with standard polypectomy or EMR. The investigators propose to perform a multicenter retrospective observational study to define the percentage of cancer in patients with GM-LSTs treated with endoscopic resection in order to evaluate the correlation between pre-resection and post-resection characteristics, defining the best therapeutic approach (en bloc or piecemeal) and avoiding incomplete endoscopic resections or unnecessary surgical procedures.

Dataset Information

Single-cell RNA profiling of colorectal granular-type laterally spreading tumor uncovers progression trajectory toward carcinoma and transcriptional signatures favoring lateral morphogenesis.

Background

Methods

Results

Conclusion

Publications

Single-cell RNA profiling of colorectal granular-type laterally spreading tumor uncovers progression trajectory toward carcinoma and transcriptional signatures favoring lateral morphogenesis.

Similar Datasets

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