Aberrant fatty acid profile and FFAR4 signaling confer endocrine resistance in breast cancer

Journal of Experimental & Clinical Cancer Research : CR
Xiao ChuYanyun Zhang

Abstract

Evidence suggests that fatty acid receptor FFAR4 plays a tumor-promoting role in adipose tissue-adjacent malignancies, but its clinical relevance remains unexplored. Here, we investigated the clinical significance and underlying mechanisms of FFAR4 in hormone receptor-positive breast cancer (HRPBC). FFAR4 expression was assessed by immunohistochemistry in an exploration cohort of 307 breast cancer cases collected from two independent institutes. Two public breast cancer microarray datasets served as validation cohorts. Gas chromatography-mass spectrometry was employed to identify FFAR4 ligands in normal and cancerous breast tissues. Survival analyses were performed in all cohorts and designated molecular subgroups. Mechanistic studies were performed in vitro in hormone receptor-positive breast cancer cell lines MCF-7 and T-47D. Aberrant FFAR4 expression and endogenous FFAR4 ligands were identified in breast cancer tissues, five FFAR4 ligands showed significantly elevated proportions in cancerous versus normal tissues. In the exploration cohort, FFAR4 was demonstrated as an independent prognostic factor for recurrences (HR: 2.183, 95% CI: 1.360-3.504, P = 0.001) and breast cancer-specific deaths (HR: 2.102, 95% CI: 1.173-3.766, ...Continue Reading

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Citations

Apr 13, 2021·Journal of Medicinal Chemistry·Gabriele CarulloAntonella Brizzi
Aug 1, 2021·Chemico-biological Interactions·Alok MishraAshutosh Shrivastava
Sep 25, 2021·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Ines BaroneSebastiano Andò
Oct 9, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ozge SaatciOzgur Sahin

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Datasets Mentioned

BETA
E-MTAB-365
GSE4922

Methods Mentioned

BETA
transfection

Software Mentioned

MSD ChemStation
R
GraphPad Prism
Affy Bioconductor
survivalROC
SPSS

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