Fatty Acid Metabolism, Oxidative phosphorylation, and cholesterol homeostasis pathways in endometrial cancer organoids

Lead Investigator: Shujie Yang, University of Iowa
Title of Proposal Research: Fatty Acid Metabolism, Oxidative phosphorylation, and cholesterol homeostasis pathways in endometrial cancer organoids
Vivli Data Request: 9141
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Obesity is a risk factor for many diseases, including at least 20 types of cancer. It is well known that obesity increases endometrial cancer (EC) risk more than any other cancer. American cancer society studies revealed that 70% of endometrial cancers are attributable to excess body weight. EC is the most common gynecologic cancer with incidence (~66,570 new cases/year) and deaths (~12,940 deaths/year) on the rise. Cancer survival has improved since the mid-1970s for all of the most common cancers except cervical and EC, which calls for major treatment advancements. The mechanisms of how obesity promote EC progression was not well understood and urgently needed. We wish to know the published data in this paper and understand Fatty Acid Metabolism, Oxidative phosphorylation, and cholesterol homeostasis pathways in EC organoids. The outstanding genes in those pathways will not only explain the mechanism of obesity driven EC, but also might serves as potential targets to prevent or inhibit obestiy driven EC, eventually leading to future treatments strategy to benefit EC patients.

Statistical Analysis Plan:

1. As we published in 2022 American Journal of Cancer Research (PMID: 36504895), the statistic analysis methods are, (1) student’s t-test will be used for comparisons of two groups. (2) all pairwise multiple comparisons will be performed by one-way ANOVA, and (3) comparisons between two groups will be performed by one-tailed two-sample student t-test with an overall significance level at 0.05 (P ≤ 0.05).
2. When we can access the data published in Fig 3C, we will rank the most altered genes.
3. We will search literature to understand the function of these genes.
4. We will also use endometrial cancer The Cancer Genome Atlas (EC-TCGA) data to confirm the expression of these genes.
5. We will also plan to confirm the expression of these genes in the endometrial tumors samples that we collected.

Requested Studies:

Genomic, Transcriptomic, and Drug Screening Data from a Pan-cancer Organoid Cohort with Source Tumor Samples
Data Contributor: Tempus Labs, Inc.
Study ID: T21.01
Sponsor ID: T21.01

Summary of results:

When my team discussed this paper (our original interest), one of my colleagues pointed out that we missed the original data. In Fig. 3C, we thought endometrial cancer organoids showed the most activation of oxidative phosphorylation, xenobiotic metabolism, and fatty acid metabolism. But, actually, this data means the difference between patients’ tumors and organoids is highest in endometrial cancer. After we realized that, we stopped going in this direction for our research.