Urinary prostaglandin E2 as a biomarker for recurrent UTI in postmenopausal women

Author:

Ebrahimzadeh Tahmineh1,Kuprasertkul Amy2,Neugent Michael L1,Lutz Kevin C3,Fuentes Jorge L2,Gadhvi Jashkaran1ORCID,Khan Fatima1,Zhang Cong3,Sharon Belle M1,Orth Kim456,Li Qiwei3,Zimmern Philippe E2,De Nisco Nicole J1ORCID

Affiliation:

1. Department of Biological Sciences, University of Texas at Dallas, Richardson, TX, USA

2. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

3. Depatment of Mathematics, University of Texas at Dallas, Richardson, TX, USA

4. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA

5. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA

6. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA

Abstract

Urinary tract infection (UTI) is one of the most common adult bacterial infections and exhibits high recurrence rates, especially in postmenopausal women. Studies in mouse models suggest that cyclooxygenase-2 (COX-2)–mediated inflammation sensitizes the bladder to recurrent UTI (rUTI). However, COX-2–mediated inflammation has not been robustly studied in human rUTI. We used human cohorts to assess urothelial COX-2 production and evaluate its product, PGE2, as a biomarker for rUTI in postmenopausal women. We found that the percentage of COX-2–positive cells was elevated in inflamed versus uninflamed bladder regions. We analyzed the performance of urinary PGE2 as a biomarker for rUTI in a controlled cohort of 92 postmenopausal women and PGE2 consistently outperformed all other tested clinical variables as a predictor of rUTI status. Furthermore, time-to-relapse analysis indicated that the risk of rUTI relapse was 3.6 times higher in women with above median urinary PGE2 levels than with below median levels. Taken together, these data suggest that urinary PGE2 may be a clinically useful diagnostic and prognostic biomarker for rUTI in postmenopausal women.

Funder

Felecia and John Cain Chair in Women’s Health

Welch Foundation

University of Texas System Rising STARs award

Once Upon a Time Foundation

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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