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 Real-world treatment patterns and outcomes in platinum-sensitive recurrent high-grade serous ovarian cancer patients

2021 ◽  
Author(s):  
Carlota Moya-Alarcón ◽  
Guiomar Piera ◽  
Ángel Callejo ◽  
Amaya Gascó
Keyword(s):  
Ovarian Cancer ◽  
Treatment Outcomes ◽  
Cancer Patients ◽  
Negative Impact ◽  
Treatment Patterns ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Wild Type ◽  
Platinum Sensitive ◽  
Study Results

Aim: To describe the overall cancer-related healthcare utilization patterns, treatment patterns and outcomes in women diagnosed with platinum-sensitive recurrent high-grade serous ovarian cancer. Patients & methods: Subanalysis of the Spanish sample of a retrospective, noninterventional, multinational, observational study. Results: BRCA-mutated patients had better outcomes in terms of progression-free survival and overall survival than patients who were BRCA wild-type. It was observed that patients’ treatment outcomes after the first recurrence progressively worsened as the patient underwent subsequent chemotherapy lines. Healthcare resource utilization when accounting for the follow-up time did not substantially differ between BRCA1/ 2-mutated and BRCA wild-type patients. Conclusion: BRCA1/2 mutation carriers have better treatment outcomes, including longer survival, without a negative impact on the use of healthcare resources.

scholarly journals High Serpin Family A Member 10 Expression Confers Platinum Sensitivity and Is Associated With Survival Benefit in High-Grade Serous Ovarian Cancer: Based on Quantitative Proteomic Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenwen Guo ◽  
Xue He ◽  
Jing Ni ◽  
Liya Ma ◽  
Xianzhong Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Gene Set ◽  
Platinum Sensitivity ◽  
Platinum Sensitive ◽  
Platinum Resistant ◽  
Sensitive Group

This study aims to identify differentially expressed proteins related with platinum sensitivity and to find biomarkers for predicting platinum response and survival outcomes in patients with high-grade serous ovarian cancer (HGSOC). Eligible HGSOC patients were divided into platinum-sensitive and platinum-resistant groups according to platinum-free interval (PFI). Tissue protein lysates from tumor tissues were subjected to an in-solution tryptic digest followed by tandem mass tag (TMT) labeling of the resulting peptides and mass spectrometric analysis. Candidate proteins were identified using differentially expressed protein and gene set enrichment analysis (GSEA) and confirmed by immunohistochemistry (IHC), and their survival relevance was evaluated in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. The results showed that there was a significant difference in the protein expression profiling between the two patient groups. In the GSEA model, a gene set of 239 extracellular matrix (ECM)-related proteins was significantly enriched in the platinum-sensitive group [normalized enrichment score (NES) = 3.82, q &lt; 10−5], and this finding was confirmed in TCGA ovarian cancer cohort. Interestingly, an ECM-related gene expression, serpin family A member 10 (SERPINA10), was identified to be significantly positively correlated with overall survival (OS) and progression-free survival (PFS) in TCGA ovarian cancer cohort (all p &lt; 0.05). IHC results demonstrated that HGSOC patients with high SERPINA10 expression had longer PFI than the patients with low SERPINA10 expression (9 vs. 5 months, p = 0.038), and the SERPINA10 expression had an area under the receiver operating characteristic curve (AUC) value of 0.758 (95% CI = 0.612–0.905; p = 0.005) to discriminate the platinum-sensitive group from the platinum-resistant group. In conclusion, the results suggested that SERPINA10 could be a promising biomarker for predicting the response and survival in platinum-based chemotherapy of HGSOC.

scholarly journals High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes

Radiology ◽  
2017 ◽  
Vol 285 (2) ◽  
pp. 472-481 ◽  
Author(s):  
Stephanie Nougaret ◽  
Yulia Lakhman ◽  
Mithat Gönen ◽  
Debra A. Goldman ◽  
Maura Miccò ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcomes ◽  
Brca Mutation ◽  
Ct Imaging ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mutation Status

scholarly journals Development of a Genomic Signatures-Based Predictor of Initial Platinum-Resistance in Advanced High-Grade Serous Ovarian Cancer Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yuan Li ◽  
Xiaolan Zhang ◽  
Yan Gao ◽  
Chunliang Shang ◽  
Bo Yu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Predictive Accuracy ◽  
Predictive Performance ◽  
Platinum Resistance ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Single Nucleotide Variants ◽  
Tissue Samples ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet.MethodsNinety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients.ResultsA high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1–100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%.ConclusionsA multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

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
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