Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Caroline H. Johnson

Second Advisor

Ying Chen

Abstract

Background: Colorectal cancer liver metastasis (CRLM) is a major cause of death in colorectal cancer, and growing evidence suggests that sex may influence tumor biology and metabolism. However, sex-specific metabolic changes in CRLM remain poorly understood.Method: This study performed sex-stratified metabolomics analysis of CRLM tissue samples using datasets generated from HILIC and RPLC LC-MS acquisition modes. Differential metabolites were identified using Wilcoxon tests with FDR correction, and pathway enrichment analysis was conducted using MetaboAnalyst to compare shared and sex-specific metabolic patterns between male and female samples. Results: Both male and female CRLM samples showed metabolic alterations in shared pathways, including one-carbon metabolism, purine metabolism, carbohydrate interconversion, and amino acid metabolism. Male samples showed additional sex-specific pathway changes related to energy metabolism, redox balance, and lipid metabolism, while no female-only enriched pathway was identified after reanalysis, although alanine, aspartate and glutamate metabolism showed relatively higher impact in females. Conclusion: In conclusion, CRLM showed both shared and sex-specific metabolic alterations. Male-associated changes appeared to involve broader functions related to energy metabolism, redox balance, lipid remodeling, and anabolic support, whereas female-associated changes were more concentrated in core amino acid- and nitrogen-related processes. In addition, the significant alteration of several putatively exposure-related metabolites suggests that CRLM metabolism may also be influenced by diet, medication, and environmental factors, highlighting the need for more comprehensive evaluation of patient background in future studies.

Comments

This is an Open Access Thesis.

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