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(OR09-06-26) The Effect of Vitamin E Delta-Tocotrienol on Mutated Apc and Kras Associated Changes in Plasma Metabolome in a Mouse Model of Colorectal Cancer

Sunday, July 26, 2026
11:30 AM - 11:42 AM ET
Location: Maryland Ballroom D

    Presenting Author(s)

  • SS

    Stefania W. Setyaningtyas, MPH

    Graduate Student
    Purdue University
    Lafayette, Indiana, United States

    Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • SI

    Suji Im

    Purdue University, United States

  • QJ

    Qing Jiang

    Purdue University, United States

Disclosure(s):
Stefania W. Setyaningtyas, MPH: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Metabolic dysregulation is a hallmark of cancer. Mutated APC and KRAS genes are frequently found in colorectal cancer (CRC) patients and co-occurring mutations of these genes are associated with poor prognosis. We recently established a genetically engineered CRC model in mice with colon specific mutations of Apc and Kras, i.e., the Apc+/580S, KrasG12D+/LSL, CACCre/+ (AKC) model. The AKC mice spontaneously develop adenoma tumors in the large intestine, thus representing early-stage CRC. The goal of this study is to delineate plasma metabolome of the AKC mice and to determine the effect of vitamin E delta-tocotrienol (dTE) on metabolic profiling in this model.

Methods: We randomly assigned 5.5-week-old AKC mice via age- and body weight-matching into the control and dTE groups, which were fed AIN93G and dTE-supplement (0.04% diet) diets, respectively. We used Apc+/580S, KrasG12D+/LSL, CAC-/- mice as wildtype (WT) controls. After four-week feeding with these diets, we collected the plasma samples, which were used for untargeted metabolomic analyses using Q-TOF. Subsequent metabolite annotation and analyses were performed using MS-DIAL and MetaboAnalyst software.

Results: We found 2253 distinct metabolites with 822 annotated compounds. Plasma samples from the AKC mice had 172 significantly changed metabolites compared to the WT controls. Among these metabolites, AKC plasmas had significantly elevated uric acids (fold change (FC) =6.8; p =0.002) and decreased lysophosphatidylcholine (LPC) 18:2 (FC = 0.4; p=0.004). Supplementation of dTE significantly increased 1-Stearoyl-sn-glycero-3-phosphocholine (18:0 Lyso-PC) (FC =2.7; p=0.033) compared to the AKC controls.

Conclusions: Co-occurring mutations of the Apc and Kras genes in the colon significantly altered metabolomic profile in mice including decrease in LPC 18:2, aligning with the observation in CRC patients. Supplementation of dTE increased 18:0 Lyso-PC, which has been shown to have anti-cancer properties.

Funding Sources: NIH/NCI R03CA283236-01A1, USDA Hatch 1022869, PICR pilot funding