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<p>Intestinal adenomas are premalignant lesions that develop into colorectal cancer (CRC), yet the metabolic pathways underlying their malignant transformation remain poorly characterized. Using targeted metabolomics via ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we found that serum levels of the bioactive lipid metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET) were dramatically elevated in <i>Apc</i><sup>Min/+</sup> adenoma model mice as early as pre-adenoma stages, compared to C57BL/6 controls. The results were also consistent in adenomas and CRC patients. ELISA data and bioinformatics analyses revealed both elevated serum 14,15-EET levels and upregulated cytochrome P450 2J2 (CYP2J2) expression in tumor. Functional studies showed that 14,15-EET accelerates adenoma growth in vivo, and promotes proliferation, migration, and invasion in vitro by activating AKT (Ser473)/ERK1/2 signaling and inducing epithelial-mesenchymal transition (EMT). Its early elevation in premalignant lesions, and relative molecules 14,15-EET/CYP2J2 represents a novel strategy for disrupting adenoma-carcinoma transition, and offering new biomarker for CRC prevention.</p>

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14,15-epoxyeicosatrienoic acid drives intestinal adenoma growth and its value as an early biomarker for intestinal adenoma occurrence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月11日

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  • Shihui He,
  • Ruyu Zeng,
  • Bobing Zheng,
  • Lingbi Jiang,
  • Jinghong Zhu,
  • Jiangchao Li

摘要

Intestinal adenomas are premalignant lesions that develop into colorectal cancer (CRC), yet the metabolic pathways underlying their malignant transformation remain poorly characterized. Using targeted metabolomics via ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we found that serum levels of the bioactive lipid metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET) were dramatically elevated in ApcMin/+ adenoma model mice as early as pre-adenoma stages, compared to C57BL/6 controls. The results were also consistent in adenomas and CRC patients. ELISA data and bioinformatics analyses revealed both elevated serum 14,15-EET levels and upregulated cytochrome P450 2J2 (CYP2J2) expression in tumor. Functional studies showed that 14,15-EET accelerates adenoma growth in vivo, and promotes proliferation, migration, and invasion in vitro by activating AKT (Ser473)/ERK1/2 signaling and inducing epithelial-mesenchymal transition (EMT). Its early elevation in premalignant lesions, and relative molecules 14,15-EET/CYP2J2 represents a novel strategy for disrupting adenoma-carcinoma transition, and offering new biomarker for CRC prevention.