scholarly journals Role of tumor location on high-grade serous ovarian cancer prognosis

2021 ◽  
Author(s):  
Seval Ay ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Özgecan Dülgar ◽  
Serdar Arıcı ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Location ◽  
Cancer Prognosis ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Ovarian Cancer Prognosis

scholarly journals AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 304
Author(s):  
Eros Azzalini ◽  
Domenico Tierno ◽  
Michele Bartoletti ◽  
Renzo Barbazza ◽  
Giorgio Giorda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Acquired Resistance ◽  
Digital Pcr ◽  
Parp Inhibitors ◽  
Clinicopathological Features ◽  
Cancer Prognosis ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Akt Isoforms ◽  
Ovarian Cancer Prognosis

High-grade serous ovarian cancer (HGSOC) is among the deadliest gynecological malignancies. The acquired resistance to platinum-based therapies and the intrinsic heterogeneity of the disease contribute to the low survival rate. To improve patients’ outcomes, new combinatorial approaches able to target different tumor vulnerabilities and enhance the efficacy of the current therapies are required. AKT inhibitors are promising antineoplastic agents able to act in synergy with PARP inhibitors, but the spectrum of patients who can benefit from this combination is unclear, since the role of the three different isoforms of AKT is still unknown. Here, we study the expression of AKT isoforms on a retrospective cohort of archive tissue by RT-droplet digital PCR (ddPCR) analyzing their association with the clinicopathological features of patients. Based on AKT1/AKT2 and AKT1/AKT3 ratios, we define four AKT classes which were related to patients’ survival, tumor morphology and BRCA1 expression. Moreover, our results show that high AKT3 expression levels were frequently associated with tumors having classic features, a low number of mitoses and the presence of psammoma bodies. Overall, our study obtains new insights on AKT isoforms and their associations with the clinicopathological features of HGSOC patients. These evidences could help to better define the subsets of patients who can benefit from AKT and PARP inhibitors therapy in future clinical trials.

scholarly journals KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Marta De Donato ◽  
Gabriele Babini ◽  
Simona Mozzetti ◽  
Marianna Buttarelli ◽  
Alessandra Ciucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Marker ◽  
Late Stage ◽  
Therapeutic Target ◽  
Family Members ◽  
High Grade ◽  
Serous Ovarian Cancer

Abstract Background In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way. Methods To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors. Results Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts. Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction. Conclusions Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.

Abstract B71: Investigating the role of PAX8 in modulating the tumor microenvironment of high-grade serous ovarian cancer

2020 ◽  
Author(s):  
Amrita Salvi ◽  
Laura Hardy ◽  
Samantha Watry ◽  
Melissa Pergande ◽  
Stephanie M. Cologna ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals Examining the interaction between TGFBR3 and ESRRA in ovarian cancer prognosis

2016 ◽  
Author(s):  
Alun Passey ◽  
Robert Brown ◽  
Charlotte S. Wilhelm-Benartzi
Keyword(s):  
Ovarian Cancer ◽  
Conflicts Of Interest ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Serous Ovarian Cancer ◽  
Cancer Genome Atlas ◽  
A Cell ◽  
Funding Support ◽  
Functional Investigation ◽  
Ovarian Cancer Prognosis

ABSTRACTThe authors found that ESRRA when co-expressed at high levels with TGFβR3 may be prognostic for serous ovarian cancer overall survival in data from the Cancer Genome Atlas; however, this result was not validated in further datasets. A cell line was also identified in this study for future functional investigation of interactions between ESRRA and TGFβR3 in the context of oestrogen signaling in order to further elucidate their potential roles as prognostic biomarkers for serous ovarian cancer.FUNDING SUPPORTThis work was supported by Cancer Research UK program A6689 (RB and CSWB) and the Medical Research Council (AP)CONFLICT OF INTEREST DISCLOSURESThe authors have declared no conflicts of interest.AUTHOR CONTRIBUTIONSCSWB designed the study. AP, CSWB, and RB developed the methodology. AP and CSWB collected the data. AP, CSWB, and RB wrote the manuscript. CSWB is responsible for the overall content.

scholarly journals Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 55
Author(s):  
Francesco Plotti ◽  
Corrado Terranova ◽  
Federica Guzzo ◽  
Carlo De Cicco Nardone ◽  
Daniela Luvero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Predictive Marker ◽  
Chemotherapy Response ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Wild Type ◽  
Platinum Sensitive ◽  
Platinum Resistant

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.

scholarly journals Abstract 3071: The role of Apela in high-grade serous ovarian cancer

2018 ◽  
Author(s):  
Laura R. Daily ◽  
Debolina Ganguly ◽  
D Neil Hayes ◽  
Yinan Wang ◽  
Michelle M. Sims ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Grade ◽  
Serous Ovarian Cancer
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