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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Colorectal Cancer | Research

Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high

Authors: Junwen Cai, Yuting Yang, Leilei Zhang, Yangyang Fang, Yanjun Zhang, Mingyue Tan, Juan Zhang, Chen Tang, Haitao Ren, Lanni Wang, Guangxin Xiang, Feng Xu, Linhua Lan, Liyi Li, Xiaoqun Zheng

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes.

Methods

Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram.

Results

This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance.

Conclusion

Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.
Appendix
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Metadata
Title
Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high
Authors
Junwen Cai
Yuting Yang
Leilei Zhang
Yangyang Fang
Yanjun Zhang
Mingyue Tan
Juan Zhang
Chen Tang
Haitao Ren
Lanni Wang
Guangxin Xiang
Feng Xu
Linhua Lan
Liyi Li
Xiaoqun Zheng
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12332-4

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