Ovarian Cancer: A Heterogeneous Disease

Kossaï, Myriam; Leary, Alexandra; Scoazec, Jean‐Yves; Genestie, Catherine

doi:10.1159/000479006

Cited by 267 publications

(237 citation statements)

References 58 publications

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“…Despite the heterogeneity observed in OC, all cases are treated as a single disease (20,21). The standard treatment is an invasive surgery followed by platinum-taxane chemotherapy.…”

Section: ' Discussionmentioning

confidence: 99%

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

Braga

Gonçales

Furtado

et al. 2020

Clinics

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The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines. METHODS: To determine the IC 50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC 50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines. CONCLUSION: SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.

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“…Despite the heterogeneity observed in OC, all cases are treated as a single disease (20,21). The standard treatment is an invasive surgery followed by platinum-taxane chemotherapy.…”

Section: ' Discussionmentioning

confidence: 99%

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

Braga

Gonçales

Furtado

et al. 2020

Clinics

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“…The standard treatment for EOC is cytoreductive surgery combined with chemotherapy. However, most EOC patients relapse and the 5-year survival rate is no more than 35% [3]. The unsatisfying outcome of EOC treatment is attributed to late diagnosis and chemotherapy resistance [4].…”

Section: Introductionmentioning

confidence: 99%

Functional polymorphisms in FOXC2 gene and Epithelial ovarian Cancer susceptibility in Chinese population

Zhou

Zou

et al. 2020

J Ovarian Res

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Background: Epithelial ovarian cancer (EOC) is highly lethal gynecological cancer. Forkhead Box Protein C2 (FOXC2) promotes occurrence and development of various malignant tumors. The present study is aimed at exploring the correlation between the polymorphism of FOXC2 and epithelial ovarian cancer susceptibility in Chinese Han population. Methods: A case-control design was used to verify the association between FOXC2 polymorphisms and epithelial ovarian cancer. The genotyping was performed using Taqman® SNP Genotyping kit by qRT-PCR. The genetic variants including rs3751794 C > T, rs1035550 A > G, rs4843163 C > G and rs4843396 C > T in FOXC2 gene were analyzed. The strength of the associations was detected using odds ratios and 95% confidence intervals. Stratification analyses showed the association between the FOXC2 gene polymorphisms rs3751794 C > T, rs4843163 C > G and rs4843396 C > T with epithelial ovarian cancer susceptibility in terms of age, metastasis status, clinical stage, pathological grade, pregnant times, pausimenia, and the expression of ER, PR, wild p53 and mutant p53. Results: Rs3751794 C > T (P = 0.0016), rs4843163 C > G (P < 0.0001) and rs4843396 C > T (P < 0.0001) were significantly associated with increased epithelial ovarian cancer risk. In stratification analyses,rs3751794 C > T, was identified to be dominant in no metastasis patients, clinical stage 4 group, middle grade pathological stage, pregnant time over 3 patients, post-menopause women, strong wild type p53 expression; rs4843163 C > G was dominant in high grade clinical stage, high grade pathological stage, post-menopause women, strong ER expression group and no mutant p53 expression group; rs4843396 C > T was dominant in high grade clinical stage, high grade pathological stage, strong ER expression group. The rs1035550 A > G was not related to epithelial ovarian cancer susceptibility. Conclusions:The results of the current study verified that FOXC2 gene polymorphisms were associated with increased epithelial ovarian cancer risk and suggested that FOXC2 gene polymorphisms might be a potential biomarker for epithelial ovarian cancer susceptibility.

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“…[3][4][5][6] Epithelial ovarian carcinomas (EOC) are classified as serous, mucinous, endometrioid, and clear-cell histology, being distinguished in terms of phenotype, molecular background, and etiology. 7 Research to identify new molecular prognostic markers needs to take this heterogeneity of ovarian cancer into account. A better understanding of the differences between ovarian cancer subtypes appears crucial to enable new diagnostic and therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

<p>Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology</p>

Czogalla¹,

Kahaly²,

Mayr³

et al. 2019

CMAR

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Purpose: This study aimed to investigate the potential prognostic impact of nuclear factor erythroid 2-related factor 2 (NRF2) and progesterone receptor A (PRA)/progesterone receptor B (PRB) in ovarian cancer patients which might be the rationale for putative new treatment strategies. Patients and methods: The presence of NRF2 and PRA/PRB was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining of NRF2 and PRA/ PRB was rated using the semi-quantitative immunoreactive score (IR score, Remmele's score) and correlated to clinical and pathological data. NRF2 and PRA/PRB expression were compared with respect to the overall survival (OS). Results: NRF2 staining was different in both, the cytoplasm and nucleus between the histological subtypes (p=0.001 and p=0.02, respectively). There was a significant difference in the PRA expression comparing all histological subtypes (p=0.02). Histological subtypes showed no significant differences in the PRB expression. A strong correlation of cytoplasmic NRF2 and PRA expression was detected (cc=0.247, p=0.003) as well as of cytoplasmic NRF2 and PRB expression (cc=0.25, p=0.003), confirmed by immunofluorescence double staining. Cytoplasmic NRF2 expression was associated with a longer OS (median 50.6 vs 32.5 months; p=0.1) as it was seen for PRA expression (median 63.4 vs 33.1 months; p=0.08), although not statistically significant. In addition, high PRB expression (median 80.4 vs 32.5 months; p=0.04) and concurrent expression of cytoplasmic NRF2 and PRA were associated with a significantly longer OS (median 109.7 vs 30.6 months; p=0.02). The same relationship was also noted for NRF2 and PRB with improved OS for patients expressing both cytoplasmic NRF2 and PRB (median 153.5 vs 30.6 months; p=0.009). Silencing of NFE2L2 induced higher mRNA expression of PGR in the cancer cell line OVCAR3 (p>0.05) confirming genetic interactions of NRF2 and PR. Conclusion: In this study, the combination of cytoplasmic NRF2 and high PRA/PRB expression was demonstrated to be associated with improved overall survival in ovarian cancer patients. Further understanding of interactions within the NRF2/AKR1C1/PR pathway could open new additional therapeutic approaches.

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Ovarian Cancer: A Heterogeneous Disease

Cited by 267 publications

References 58 publications

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

Functional polymorphisms in FOXC2 gene and Epithelial ovarian Cancer susceptibility in Chinese population

<p>Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology</p>

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