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.

scholarly journals Identification of Novel Fusion Transcripts in High Grade Serous Ovarian Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4791
Author(s):  
Andreea Newtson ◽  
Henry Reyes ◽  
Eric J. Devor ◽  
Michael J. Goodheart ◽  
Jesus Gonzalez Bosquet
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Dna Sequences ◽  
Chromosomal Rearrangements ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Fallopian Tubes ◽  
Fusion Transcripts ◽  
Analytical Platforms

Fusion genes are structural chromosomal rearrangements resulting in the exchange of DNA sequences between genes. This results in the formation of a new combined gene. They have been implicated in carcinogenesis in a number of different cancers, though they have been understudied in high grade serous ovarian cancer. This study used high throughput tools to compare the transcriptome of high grade serous ovarian cancer and normal fallopian tubes in the interest of identifying unique fusion transcripts within each group. Indeed, we found that there were significantly more fusion transcripts in the cancer samples relative to the normal fallopian tubes. Following this, the role of fusion transcripts in chemo-response and overall survival was investigated. This led to the identification of fusion transcripts significantly associated with overall survival. Validation was performed with different analytical platforms and different algorithms to find fusion transcripts.

scholarly journals Building in vitro 3D human multicellular models of high-grade serous ovarian cancer

2022 ◽  
Vol 3 (1) ◽  
pp. 101086
Author(s):  
Beatrice Malacrida ◽  
Oliver M.T. Pearce ◽  
Frances R. Balkwill
Keyword(s):  
Ovarian Cancer ◽  
High Grade ◽  
Serous Ovarian Cancer

Cyclin E as a potential therapeutic target in high grade serous ovarian cancer

2016 ◽  
Vol 143 (1) ◽  
pp. 152-158 ◽  
Author(s):  
J. Kanska ◽  
M. Zakhour ◽  
B. Taylor-Harding ◽  
B.Y. Karlan ◽  
W.R. Wiedemeyer
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Target ◽  
Cyclin E ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Potential Therapeutic Target

Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer

2016 ◽  
Vol 26 (4) ◽  
pp. 671-679 ◽  
Author(s):  
Hans-Christian Bösmüller ◽  
Philipp Wagner ◽  
Janet Kerstin Peper ◽  
Heiko Schuster ◽  
Deborah Lam Pham ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Prognostic Value ◽  
Intraepithelial Lymphocytes ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Term Survival ◽  
Cell Counts

ObjectiveIncreased numbers of tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103+ TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC.MethodsThe density of intratumoral CD3+ and CD103+ lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4+, CD8+, CD56+, FoxP3+, and TCRγ+ T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome.ResultsBoth the presence of CD103+ cells, as well as high numbers of intraepithelial CD3+ lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3high/CD103high tumors showed a 5-year survival rate at 90%, CD3low/CD103high at 63%, and CD3low/CD103low at 0% (P < 0.001).ConclusionsThese results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.

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 Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 966 ◽  
Author(s):  
Marianna Buttarelli ◽  
Marta De Donato ◽  
Giuseppina Raspaglio ◽  
Gabriele Babini ◽  
Alessandra Ciucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Biology ◽  
Tissue Level ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Clinical Value ◽  
Pre Treatment ◽  
Phosphatase And Tensin Homologue

Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a prognostic marker in high-grade serous ovarian cancer (HGSOC), the most common and deadliest gynecologic malignancy. To the aim of the study, we measured MEG3 transcript levels in 90 pre-treatment peritoneal biopsies. We also investigated MEG3 function in ovarian cancer biology. We found that high MEG3 expression was independently associated with better progression-free (p = 0.002) and overall survival (p = 0.01). In vitro and in vivo preclinical studies supported a role for MEG3 as a tumor suppressor in HGSOC, possibly through modulation of the phosphatase and tensin homologue (PTEN) network. Overall, results from this study demonstrated that decreased MEG3 is a hallmark for malignancy and tumor progression in HGSOC.

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