1. High-fat diet and obesity are associated with differential angiogenic gene expression in epithelial ovarian cancer.
- Author
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Baumann KE, Siamakpour-Reihani S, Dottino J, Dai Y, Bentley R, Jiang C, Zhang D, Sibley AB, Zhou C, Berchuck A, Owzar K, Bae-Jump V, and Secord AA
- Subjects
- Humans, Mice, Animals, Female, Carcinoma, Ovarian Epithelial genetics, Carcinoma, Ovarian Epithelial complications, Obesity genetics, Obesity complications, Gene Expression, Biomarkers, Mice, Inbred C57BL, Diet, High-Fat adverse effects, Ovarian Neoplasms genetics, Ovarian Neoplasms complications
- Abstract
Objective: We sought to evaluate the association between diet and angiogenic biomarkers in KpB mice, and the association between these markers, body mass index (BMI), and overall survival (OS) in high-grade serous cancers (HGSC)., Methods: Tumors previously obtained from KpB mice subjected to high-fat diets (HFD, n = 10) or low-fat diets (LFD, n = 10) were evaluated for angiogenesis based on CD-31 microvessel density (MVD). Data from prior microarray analysis (Agilent 244 K arrays) conducted in 10 mice were utilized to assess associations between diet and angiogenetic biomarkers. Agilent (mouse) and Affymetrix Human Genome U133a probes were linked to 162 angiogenic-related genes. The associations between biomarkers, BMI, and OS were evaluated in an HGSC internal database (IDB) (n = 40). Genes with unadjusted p < 0.05 were evaluated for association with OS in the TCGA-OV database (n = 339)., Results: There was no association between CD-31 and diet in mice (p = 0.66). Sixteen angiogenic-related genes passed the p < 0.05 threshold for association with HFD vs. LFD. Transforming growth factor-alpha (TGFA) demonstrated 72% higher expression in HFD vs. LFD mice (p = 0.04). Similar to the mouse study, in our HGSC IDB, higher TGFA expression correlated with higher BMI (p = 0.01) and shorter survival (p = 0.001). In the TCGA-OV dataset, BMI data was not available and there was no association between TGFA and OS (p = 0.48)., Conclusions: HFD and obesity may promote tumor progression via differential modulation of TGFA. We were unable to confirm this finding in the TCGA dataset. Further evaluation of TGFA is needed to determine if this is a target unique to obesity-driven HGSC., Competing Interests: Declaration of Competing Interest Dr. Alvarez Secord discloses that she has received clinical trial grant funding from AbbVie, Aravive, Astra Zeneca,Clovis, Eisai, Ellipses Pharma, Tesaro/GSK, I-MAB Biopharma, Immunogen, Merck, OncoQuest, Roche/Genentech, Seagen Inc.,VBL Therapeutics, and National Cancer Trial Network. She has participated in Advisory Boards (uncompensated) for AbbVie, Aravive, AstraZeneca, Clovis, GSK/Tesaro, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, OncoQuest, and Regeneron; and Clinical Trial Steering Committees (uncompensated) for the AXLerate trial (Aravive),AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio)within the past 36 months. Dr. Bae-Jump has received collaborative grants from Merck; drugs for preclinical studies from Chimerix; collaborative grants and drugs for preclinical studies from Epirium and Genentech; and participates on the Eisai Endometrial Cancer Strategic Council. The other authors declare no conflicts of interest. This work has not been previously presented or published in any format. This work has been approved by all authors and is not under consideration for publication elsewhere., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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