Comparative metabolomics reveals specific metabolic signatures in colorectal cancer cell line models

Sep 30, 2026

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Colorectal cancer (CRC) shows substantial metabolic heterogeneity that influences tumor progression and treatment response, yet systematic comparisons across widely used CRC cell lines remain limited. This study performs a comprehensive metabolomic analysis on HT-29, Caco-2, and SW480 cells to identify metabolic differences and interpret biological significance. UHPLC-MS/MS quantified intracellular and extracellular metabolites, followed by PCA and PLS-DA, and pathway enrichment to determine dysregulated routes. Twenty-five differential metabolites and three key dysregulated pathways—glycerophospholipid metabolism, ether lipid metabolism, and pantothenate and CoA biosynthesis—were identified.

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Li et al. Discover Oncology (2026) 17:26 [https://doi.org/10.1007/s12672-025-04183-7](https://doi.org/10.1007/s12672-025-04183-7) Discover Oncology RESEARCH Open Access Comparative metabolomics reveals specific metabolic signatures in colorectal cancer cell line models Manshan Li 1, Chuanyang Yu2, Zhihua Li3, Lianjie Xiong 1, Jiaru Wang 1, Xingyu Shang 1, Hehong Sun 1, Yanhong Chang 1, Xinxin Du 1* and Ran Zheng 1* *Correspondence: Xinxin Du [justindxx@163.com](justindxx@163.com)[ ](justindxx@163.com)Ran Zheng [zranran2023@163.com](zranran2023@163.com)[ ](zranran2023@163.com)1School of Life Science and Engineering, Jining University, 273199 Jining, China 2School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China 3Department of Medical Laboratory, Zoucheng People’s Hospital, Jining 273500, China Abstract Colorectal cancer (CRC) exhibits substantial metabolic heterogeneity, which plays a critical role in tumor progression and treatment response. However, systematic comparisons of metabolic profiles among widely used CRC cell lines are still lacking. Understanding these metabolic differences is essential for improving the translational relevance of preclinical studies. The study aims to conduct a comprehensive metabolomic analysis on three widely used CRC cell lines (HT-29, Caco-2, SW480) to identify their metabolic differences and explore their biological significance and origins. We conducted a metabolomic analysis using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to measure intracellular and extracellular metabolites. Multivariate statistical approaches, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were applied to identify metabolic variations. Pathway enrichment analysis was then performed to uncover dysregulated metabolic pathways. Our analysis revealed distinct metabolic profiles among the three CRC cell lines, with 25 differential metabolites identified. Pathway enrichment analysis highlighted three significantly dysregulated pathways: glycerophospholipid metabolism, ether lipid metabolism, and pantothenate and CoA biosynthesis. These findings demonstrate intrinsic metabolic heterogeneity at both intracellular and extracellular levels. These findings confirm intrinsic metabolic heterogeneity of the three CRC cell lines by intracellular and extracellular profiling, highlighting the importance of validating results across multiple models to address the limitations intrinsic to single cell lines in mechanistic and translational studies. Keywords Colorectal cancer (CRC), Cell line, Metabolomics, Metabolic heterogeneity, Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by-nc-nd/4.0/. 1 Introduction Colorectal cancer (CRC) is the third most common malignancy worldwide, with a poor five-year survival rate in a

FAQs

What is the main goal of the comparative metabolomics study?

To comprehensively analyze three widely used colorectal cancer cell lines (HT-29, Caco-2, SW480) to identify metabolic differences and explore their biological significance and origins.

Which experimental and statistical methods were used to measure and analyze metabolites?

Intracellular and extracellular metabolites were measured using UHPLC-MS/MS, with PCA and PLS-DA applied to detect metabolic variation.

Which metabolic pathways were found to be significantly dysregulated?

Pathway enrichment highlighted three significantly dysregulated pathways: glycerophospholipid metabolism, ether lipid metabolism, and pantothenate and CoA biosynthesis.

Sep 30, 2026

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