Nika Marolt (Author), Renata Pavlič (Author), Tinkara Kreft (Author), Marija Gjorgoska (Author), Tea Lanišnik-Rižner (Author)

Abstract

The high mortality rate due to chemoresistance in patients with high-grade ovarian cancer (HGSOC) emphasizes the urgent need to determine optimal treatment strategies for advanced and recurrent cases. Our study investigates the interplay between estrogens and chemoresistance in HGSOC and shows clear differences between platinum-sensitive and -resistant tumors. Through comprehensive transcriptome analyzes, we uncover differences in the expression of genes of estrogen biosynthesis, metabolism, transport and action underlying platinum resistance in different tissues of HGSOC subtypes and in six HGSOC cell lines. Furthermore, we identify genes involved in estrogen biosynthesis and metabolism as prognostic biomarkers for HGSOC. Additionally, our study elucidates different patterns of estrogen formation/metabolism and their effects on cell proliferation between six HGSOC cell lines with different platinum sensitivity. These results emphasize the dynamic interplay between estrogens and HGSOC chemoresistance. In particular, targeting the activity of steroid sulfatase (STS) proves to be a promising therapeutic approach with potential efficacy in limiting estrogen-driven cell proliferation. Our study reveals potential prognostic markers as well as identifies novel therapeutic targets that show promise for overcoming resistance and improving treatment outcomes in HGSOC.

Keywords

high-grade serous ovarian cancer;estrogen metabolisem;prognostic biomarkers;therapeutic targets;transcriptomic analysis;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 577.2
COBISS: 202256387 Link will open in a new window
ISSN: 1950-6007
Views: 52
Downloads: 33
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Other data

Secondary language: Slovenian
Secondary keywords: serozni rak jajčnikov visoke stopnje;metabolizem estrogena;prognostični biomarkerji;terapevtske tarče;transkriptomska analiza;
Type (COBISS): Article
Pages: str. 1-17
Issue: ǂVol. ǂ177, [article no.] 117069
Chronology: Aug. 2024
DOI: 10.1016/j.biopha.2024.117069
ID: 25762690
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