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.

3rd Faculty of Medicine Charles University Ruska 87 100 00 Prague Czech Republic

Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 77 32300 Pilsen Czech Republic

Department of Cancer Genetics Institute for Cancer Research Oslo University Hospital The Norwegian Radium Hospital Oslo Norway

Department of Gynecology and Obstetrics 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Gynecology and Obstetrics Faculty of Medicine and University Hospital in Pilsen Charles University Pilsen Czech Republic

Department of Medical Genetics Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 142 00 Prague Czech Republic

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine and Motol University Hospital Charles University Prague Czech Republic

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Albertov 4 128 00 Prague Czech Republic

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 76 323 00 Pilsen Czech Republic

Toxicogenomics Unit National Institute of Public Health Srobarova 48 100 42 Prague Czech Republic

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