Targeted Metabolomic Serum Analysis of Patients with High and Low Risk of Endometrial Cancer Recurrence and Positive and Negative Lymph Node Status

TL;DR

This study identifies specific serum metabolites that could help predict endometrial cancer recurrence risk and lymph node status, potentially improving patient care.

Contribution

The study introduces novel metabolic biomarkers for endometrial cancer recurrence and lymph node status through targeted serum metabolomic profiling.

Findings

High-risk and lymph node-positive patients had lower levels of phosphatidylcholines, lysophosphatidylcholines, and specific amino acids.

Alanine and taurine showed strong diagnostic potential in distinguishing patient groups.

Metabolic reprogramming involving lipid and amino acid metabolism is linked to aggressive cancer phenotypes.

Abstract

Background: Endometrial cancer is among the most prevalent gynecological malignancies, with increasing mortality primarily due to initially advanced disease with lymph node metastasis or tumor recurrence. Current risk stratification models show limited accuracy, highlighting the need for more accurate biomarkers. This study aimed to identify metabolic compounds that can serve as predictors of recurrence risk and lymph node status in endometrial cancer. Methods: Targeted metabolomic profiling of preoperative serum samples from 123 patients with endometrial cancer, stratified into high- or low-risk and lymph node-positive or -negative groups, was conducted using the AbsoluteIDQ p180 Kit and high-performance liquid chromatography–mass spectrometry. Results: Analysis revealed significant differences in metabolites related to lipid and amino acid metabolism between groups. High-risk and lymph node-positive patients presented significantly lower concentrations of phosphatidylcholines, lysophosphatidylcholines, medium-chain acylcarnitines, and specific amino acids such as alanine, histidine, and tryptophan compared to low-risk and lymph node-negative patients. Receiver operating characteristic curve analyses highlighted the diagnostic potential of these metabolites, particularly alanine and taurine, in distinguishing patient groups. Conclusions: The findings indicate complex metabolic reprogramming associated with aggressive endometrial cancer phenotypes, involving enhanced lipid utilization and amino acid metabolism alterations, potentially supporting tumor proliferation and metastatic progression. Thus, targeted metabolomic serum profiling might be a powerful tool for improving risk assessment, enabling more personalized therapeutic approaches and management strategies in endometrial cancer.

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