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Updated: Sep 15, 2025
10:51
Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System
Published on: April 23, 2021
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Interactions Among Tumor Subtype, PPARγ Expression, and Adipose Proliferation Shape Outcomes in Breast Cancer
Aditya Shah1,2, Katie Liu1,3, Ryan Liu1,4
1Departments of Cellular & Molecular Physiology, Internal Medicine (Endocrinology), and Comparative Medicine, Yale University, New Haven, CT, United States.
Medrxiv : the Preprint Server for Health Sciences
|July 17, 2025
Summary
High PPARγ gene expression indicates better breast cancer survival, especially in premenopausal women. Adipose tissue proliferation varies by tumor subtype, suggesting targeted therapies.
Area of Science:
- Oncology
- Metabolic Research
- Genetics
Background:
- Breast cancer progression is complex, influenced by tumor biology, patient metabolism, and menopausal status.
- Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of lipid metabolism with potential roles in cancer.
- Adipose tissue metabolic activity may correlate with breast cancer subtypes and patient characteristics.
Purpose of the Study:
- To investigate the prognostic significance of PPARγ gene expression in breast cancer.
- To explore the relationship between PPARγ expression, menopausal status, and breast cancer survival.
- To examine adipose tissue proliferation markers in relation to breast cancer subtypes and patient phenotypes.
Main Methods:
- Analysis of RNA-sequencing data from the TCGA-BRCA cohort (n=1094) stratified by PPARγ expression, menopausal status, and tumor receptor status (ER+, HER2-, TNBC).
- Kaplan-Meier survival analysis to assess the association between high PPARγ expression and overall/disease-specific survival.
- Analysis of PET-CT scans (ACRIN-6888 trial, n=69) measuring 18F-FLT uptake in adipose tissue (SUV metrics) across different patient and tumor subgroups.
Main Results:
- High PPARγ expression (≥6.903 FPKM) was significantly linked to improved overall and disease-specific survival, particularly in premenopausal patients.
- Postmenopausal patients exhibited lower visceral adipose tissue SUVmean compared to premenopausal patients.
- ER+ and non-TNBC tumors were associated with significantly lower adipose tissue SUVpeak and SUVmax, indicating metabolic reprogramming.
Conclusions:
- PPARγ is a potential therapeutic target in breast cancer, modulating lipid metabolism and influencing patient outcomes.
- Adipose tissue proliferation and metabolic activity are reprogrammed based on breast cancer subtype and patient menopausal status.
- These findings support the development of subtype-specific therapeutic strategies targeting metabolic pathways in breast cancer.
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