The expression and clinical significance of ERβ/ERα in ovarian cancer: can we predict the effectiveness of platinum plus taxane therapy?

Богуш, Т. А.; Башарина, А. А.; Богуш, Е. А.; Scherbakov, Alexander M.; Давыдов, М. М.; Косоруков, В. С.

doi:10.1007/s11845-021-02842-6

Cited by 6 publications

(4 citation statements)

References 56 publications

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“…However, our results showed that high levels of ERβ and the downstream RERG induced epithelial cell apoptosis and lacrimal gland atrophy, while low levels of ERβ and RERG induced lymphocyte proliferation (Figures 1B, 2, 5). Meanwhile, different subtypes of ER have distinct effects on survival: ERβ is associated with tumor suppression and better survival outcomes (51,52), whereas high expression of ERα is associated with poor survival outcomes (53,54). This observation is also reflected in our results, as ERα is low or not expressed in LGBLEL, and the dominant location of ERβ (Figure 1B) appears to be one of the reasons that LGBLEL is a benign epithelial tumor.…”

Section: Discussionsupporting

confidence: 77%

Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL

Zhang

Zhao

et al. 2023

Front. Med.

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PurposeLacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4-related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset.MethodsSeventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development.ResultsThe serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERβ and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ERα was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis.ConclusionTherefore, the tissue-heterogeneous expression pattern of ERβ is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.

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Section: Discussionsupporting

confidence: 77%

Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL

Zhang

Zhao

et al. 2023

Front. Med.

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“…Interestingly, a high level of ERβ, and not ERα, expression in stage III HGSOC patients can predict the efficacy of platinum plus taxane chemotherapy. Compared to ERβ low expression group, the high ERβ expression group exhibited a 2 times greater median progression-free survival and a 2.2 times less recurrence risk [53], and the status of ERβ can be considered as one of the possible predictors for evaluating the effectiveness of OCa therapy [53]. Importantly, knockdown of ERβ confirmed resistance, whereas overexpression enhanced sensitivity to diosmetin [45].…”

Section: Discussionmentioning

confidence: 97%

Therapeutic Targeting of Ovarian Cancer Stem Cells Using Estrogen Receptor Beta Agonist

Alejo

Venkata

et al. 2022

IJMS

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Ovarian cancer (OCa) is the deadliest gynecologic cancer. Emerging studies suggest ovarian cancer stem cells (OCSCs) contribute to chemotherapy resistance and tumor relapse. Recent studies demonstrated estrogen receptor beta (ERβ) exerts tumor suppressor functions in OCa. However, the status of ERβ expression in OCSCs and the therapeutic utility of the ERβ agonist LY500307 for targeting OCSCs remain unknown. OCSCs were enriched from ES2, OV90, SKOV3, OVSAHO, and A2780 cells using ALDEFLUOR kit. RT-qPCR results showed ERβ, particularly ERβ isoform 1, is highly expressed in OCSCs and that ERβ agonist LY500307 significantly reduced the viability of OCSCs. Treatment of OCSCs with LY500307 significantly reduced sphere formation, self-renewal, and invasion, while also promoting apoptosis and G2/M cell cycle arrest. Mechanistic studies using RNA-seq analysis demonstrated that LY500307 treatment resulted in modulation of pathways related to cell cycle and apoptosis. Western blot and RT-qPCR assays demonstrated the upregulation of apoptosis and cell cycle arrest genes such as FDXR, p21/CDKN1A, cleaved PARP, and caspase 3, and the downregulation of stemness markers SOX2, Oct4, and Nanog. Importantly, treatment of LY500307 significantly attenuated the tumor-initiating capacity of OCSCs in orthotopic OCa murine xenograft models. Our results demonstrate that ERβ agonist LY500307 is highly efficacious in reducing the stemness and promoting apoptosis of OCSCs and shows significant promise as a novel therapeutic agent in treating OCa.

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“…GI, as a surrogate of HRD, has risen as a prognostic and predictive tool in HGSOC [27]. While HRR-based stratification, based on any alteration or effect in the genome, is widely recognized as essential, many efforts have been made to develop and clinically validate academic tools based on different approaches [28][29][30]. In this study, we developed three single-source models based on SNPs, GI, and RNA expression analysis, respectively, and an integrative ensemble model (the Scarface score) to predict response to DNA-damaging agents-particularly platinum-based chemotherapy and PARPis.…”

Section: Discussionmentioning

confidence: 99%

The Scarface Score: Deciphering Response to DNA Damage Agents in High-Grade Serous Ovarian Cancer—A GEICO Study

Fernández-Serra

López-Reig

Marquez

et al. 2023

Cancers

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Genomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87–159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.

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The expression and clinical significance of ERβ/ERα in ovarian cancer: can we predict the effectiveness of platinum plus taxane therapy?

Cited by 6 publications

References 56 publications

Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL

Missing link between tissue specific expressing pattern of ERβ and the clinical manifestations in LGBLEL

Therapeutic Targeting of Ovarian Cancer Stem Cells Using Estrogen Receptor Beta Agonist

The Scarface Score: Deciphering Response to DNA Damage Agents in High-Grade Serous Ovarian Cancer—A GEICO Study

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