Search the repository

A+ | A- | | SLO | ENG

Abstract: Ovarian cancer (OC), particularly high-grade serous carcinoma (HGSC), is a leading cause of gynecological cancer mortality due to late diagnosis and chemoresistance. While studies on OC cell lines have shown that overexpression of the ATP7A membrane transporter correlates with resistance to platinum-based drugs (PtBMs) and cross-resistance to copper (Cu), clinical evidence is lacking. The functionality of ceruloplasmin (CP), the main Cu-transporting protein in the blood, is dependent on, among other things, ATP7A activity. This study investigated ATP7A expression and CP levels as potential biomarkers for predicting responses to PtBMs. We included 28 HGSC patients who underwent neoadjuvant chemotherapy (NACT). ATP7A expression in ovarian and peritoneal tissues before NACT and in peritoneal and omental tissues after NACT was analyzed via qPCR, and CP levels in ascites and plasma were measured via ELISA before and after NACT. In total, 54% of patients exhibited ATP7A expression in pretreatment tissue (ovary and/or peritoneum), while 43% of patients exhibited ATP7A expression in tissue after treatment (peritoneum and/or omentum). A significant association was found between higher ATP7A expression in the peritoneum before NACT and an unfavorable CA-125 elimination rate constant k (KELIM) score. Patients with omental ATP7A expression had significantly higher plasma mean CP levels before NACT. Plasma CP levels decreased significantly after NACT, and higher CP levels after NACT were associated with a shorter platinum-free interval (PFI). These findings suggest that the ATP7A transporter and CP have the potential to serve as predictive markers of chemoresistance, but further research is needed to validate their clinical utility.
Keywords: ATP7A, transporter, ceruloplasmin, ovarian cancer, high-grade serous carcinoma, chemoresistance, predictive marker
Published in DiRROS: 11.06.2026; Views: 244; Downloads: 189
Full text (1,77 MB)
This document has many files! More...

Abstract: Background: High-grade serous carcinoma (HGSC) is the most lethal of gynecological cancers in developed countries. It usually presents late with non-specific symptoms and most cases are diagnosed at an advanced stage, with 5-year overall survival being around 40%. Biomarkers for screening and early diagnosis of this aggressive disease are, thus, a research priority. Extracellular vesicles (EVs) that reflect the cell of origin and that can be isolated from local fluid and plasma by minimally invasive liquid biopsy are such promising biomarkers. Besides EV concentration and molecular profile, which have been the main focus of research for many years, recent studies have also called attention to EV size distribution. The aim of our study was to evaluate the potential of EV concentration and size distribution in local fluid and plasma as diagnostic biomarkers for HGSC. Methods: Paired pretreatment ascites and plasma samples from 37 patients with advanced HGSC and paired pretreatment free peritoneal fluid (FPF) and plasma samples from 40 controls with benign ovarian pathology (BOP) were analyzed using nanoparticle tracking analysis (NTA). Results: We observed a significant difference in EV concentration in local fluid, but not in plasma, between HGSC patients and the control group. We also found a significant difference in EV size distribution in both local fluid and plasma between HGSC patients and the control group. The receiver operating characteristics (ROC) curve analysis of EV characteristics showed excellent diagnostic performance for the mode, D10, and D50 in local fluid and acceptable diagnostic performance for EV concentration and mean EV size in local fluid, as well as for the mode and D10 value in plasma. Conclusions: The results of our study show that EV concentration in local fluid and more importantly EV size distribution in both local fluid and plasma are significantly changed in the presence of HGSC. Future research of size-dependent molecular profiling of EVs could help identify novel diagnostic biomarkers for HGSC.
Keywords: diagnostic biomarkers, extracellular vesicles, high-grade serous carcinoma, liquid biopsy, nanoparticle-tracking analysis, ovarian cancer
Published in DiRROS: 05.06.2026; Views: 303; Downloads: 206
Full text (1,20 MB)
This document has many files! More...

Abstract: High-grade serous ovarian carcinoma (HGSOC) is marked by late diagnosis and chemoresistance, partly driven by chronic inflammation and hypoxia in the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1a) is a key regulator of these processes; however, its spatial distribution, interaction with inflammation, and effect on chemotherapy response in HGSOC remain unclear. This retrospective study included 28 advanced HGSOC patients treated with neoadjuvant chemotherapy (NACT). Samples were collected at primary surgery (PS) (ovarian and peritoneal tissue, plasma, ascites) and post-NACT at interval debulking surgery (IDS) (omentum, peritoneal tissue, plasma). HIF-1a mRNA expression varied by site, with higher levels in omental and peritoneal tissues compared to ovarian tissue. Plasma and ascites concentrations were significantly correlated, although the mean ascites concentration was lower. Elevated HIF-1a concentration in ascites and plasma at baseline correlated with ESR (erythrocyte sedimentation rate) >30 mm/h, which was also correlated with BRCA mutation status. No correlation was found between HIF-1a and CRP (C-reactive protein) levels. Higher HIF-1a concentrations in ascites and plasma were linked to poor chemotherapy response (CRS1) at IDS. No significant changes in plasma HIF-1a, ESR, or peritoneal HIF-1a mRNA expression were observed before and after chemotherapy. Increased peritoneal HIF-1a at baseline showed a trend toward shorter progression-free survival. These findings suggest that HIF-1a may reflect hypoxia-inflammation crosstalk associated with chemoresistance and progression in HGSOC. The hypoxic-inflammatory microenvironment appears to persist despite chemotherapy and could contribute to ongoing disease activity. However, these observations require validation in independent cohorts before any prognostic or predictive implications can be considered.
Keywords: body fluids, chronic inflammation, HIF-1a, high-grade serous ovarian carcinoma, neoadjuvant chemotherapy, tumor tissue
Published in DiRROS: 26.03.2026; Views: 373; Downloads: 249
Full text (750,43 KB)
This document has many files! More...

Keywords: ginekologija, onkologija, ginekološka onkologija, diagnostika, zdravljenje, etiologija, epidemiologija, klinična patologija, medicinska rehabilitacija, zborniki
Published in DiRROS: 10.12.2025; Views: 1343; Downloads: 362
Full text (5,17 MB)

Abstract: The aim of the study was to analyze the overall survival (OS) and progression free survival (PFS) of patients with high grade and advanced stage epithelial ovarian cancer (EOC) with at least 60 months of follow-up treated in a single gynecologic oncology institute. We compared primary debulking surgery (PDS) versus neoadjuvant chemotherapy plus interval debulking surgery (NACT + IDS) stratifying data based on residual disease with the intent to identify the rationale for therapeutic option decision and the role of laparoscopic evaluation of resectability for that intention. Patients and methods. This is observational retrospective study on consecutive patients with diagnosis of high grade and International Federation of Gynecology and Obstetrics (FIGO) stage III/IV EOC referred to our center between January 2008 and May 2012. We selected only patients with a follow-up of at least 60 months. Primary endpoint was to compare PDS versus NACT + IDS in term of progression free survival (PFS) and overall survival (OS). Secondary endpoints were PFS and OS stratifying data according to residual disease after surgery in patients receiving PDS versus NACT + IDS. Finally, through Cox hazards models, we tested the prognostic value of different variables (patient age at diagnosis, residual disease after debulking, American Society of Anesthesiologists (ASA) stage, number of adjuvantchemotherapy cycles) for predicting OS. Results. A total number of 157 patients were included in data analysis. Comparing PDS arm (108 patients) and NACT + IDS arm (49 patients) we found no significant differences in term of OS (41.3 versus 34.5 months, respectively) and PFS (17.3 versus 18.3 months, respectively). According to residual disease we found no significant differences in term of OS between NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0 or residual disease = 1, as well as no significant differences in PFS were found comparing NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0; contrarily, median PFS resulted significantly lower in PDS patients receiving optimal debulking (residual disease = 1) in comparison to NACT + IDS patients receiving complete debulking (residual disease = 0). PDS arm was affected by a significant higher rate of severe post-operative complications (grade 3 and 4). Diagnostic laparoscopy before surgery was significantly associated with complete debulking. Conclusions. We confirm previous findings concerning the non-superiority of NACT + IDS compared to PDS for the treatment of EOC, even if NACT + IDS treatment was associated with significant lower rate of post-operative complications. On the other hand, selecting patients for NACT + IDS, based on laparoscopic evaluation of resectabilty prolongs the PFS and does not worse the OS compared to the patients not completely debulked with PDS.
Keywords: epithelial ovarian cancer, advanced stage, primary debulking surgery, interval debulking surgery
Published in DiRROS: 11.06.2024; Views: 2416; Downloads: 973
Full text (692,78 KB)
This document has many files! More...