0587724 - ÚEM 2025 RIV NL eng J - Journal Article
Tomášová, Kristýna - Šeborová, K. - Kroupa, Michal - Horák, Josef - Kavec, Miriam Julie - Vodičková, Ludmila - Rob, L. - Hrubá, M. - Mrhalová, H. - Bartáková, A. - Bouda, J. - Fleischer, T. - Kristensen, V.N. - Vodička, Pavel - Václavíková, R.
Telomere length as a predictor of therapy response and survival in patients diagnosed with ovarian carcinoma.
Heliyon. Roč. 10, č. 13 (2024), č. článku e33525. ISSN 2405-8440. E-ISSN 2405-8440
R&D Projects: GA ČR(CZ) GA19-10543S; GA ČR(CZ) GA21-27902S; GA MZd(CZ) NU21-03-00145; GA MŠMT LX22NPO5102
Institutional support: RVO:68378041
Keywords : telomere length * ovarian cancer * shelterin * telomerase * therapy response
OECD category: Oncology
Impact factor: 4, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S2405844024095562?via%3Dihub

Impaired telomere length (TL) maintenance in ovarian tissue may play a pivotal role in the onset of epithelial ovarian cancer (OvC). TL in either target or surrogate tissue (blood) is currently being investigated for use as a predictor in anti-OvC therapy or as a biomarker of the disease progression, respectively. There is currently an urgent need for an appropriate approach to chemotherapy response prediction.

We performed a monochrome multiplex qPCR measurement of TL in peripheral blood leukocytes (PBL) and tumor tissues of 209 OvC patients. The methylation status and gene expression of the shelterin complex and telomerase catalytic subunit (hTERT) were determined within tumor tissues by High-Throughput DNA methylation profiling and RNA sequencing (RNA-Seq) analysis, respectively. The patients sensitive to cancer treatment (n = 46) had shorter telomeres in PBL compared to treatment-resistant patients (n = 93, P = 0.037). In the patients with a different therapy response, transcriptomic analysis showed alterations in the peroxisome proliferator-activated receptor (PPAR) signaling pathway (q = 0.001). Moreover, tumor TL shorter than the median corresponded to better overall survival (OS) (P = 0.006). TPP1 gene expression was positively associated with TL in tumor tissue (P = 0.026).

TL measured in PBL could serve as a marker of platinum therapy response in OvC patients. Additionally, TL determined in tumor tissue provides information on OvC patients' OS.
Permanent Link: https://hdl.handle.net/11104/0354830