scholarly journals Prognostic implications of forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) in epithelial ovarian cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Gwan Hee Han ◽  
Doo Byung Chay ◽  
Sanghee Nam ◽  
Hanbyoul Cho ◽  
Joon-Yong Chung ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Hazard Ratio ◽  
Ovarian Tumors ◽  
High Expression ◽  
Epithelial Tissues ◽  
Forkhead Box ◽  
High Hazard Ratio

Abstract Background Transcription factors forkhead box protein O1 (FOXO1) and paired box 3 (PAX3) have been reported to play important roles in various cancers. However, their role in epithelial ovarian cancer (EOC) has not been elucidated yet. Therefore, we evaluated the expression and clinical significance of FOXO1 and PAX3 in EOC. Methods Immunohistochemical analyses of FOXO1 and PAX3 in 212 EOCs, 57 borderline ovarian tumors, 153 benign epithelial ovarian tumors, and 79 nonadjacent normal epithelial tissues were performed using tissue microarray. Various clinicopathological variables, including the survival of EOC patients, were compared. In addition, the effect of FOXO1 on cell growth was assessed in EOC cell lines. Results FOXO1 and PAX3 protein expression levels were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues, and borderline tumors (all p < 0.001). In EOC tissues, FOXO1 expression was positively correlated with PAX3 expression (Spearman’s rho = 0.118, p = 0.149). Multivariate survival analysis revealed that high FOXO1 expression (hazard ratio = 2.77 [95% CI, 1.48–5.18], p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed a high hazard ratio (4.60 [95% CI, 2.00–10.55], p < 0.001) for overall survival. Also in vitro results demonstrated that knockdown of FOXO1 was associated with decreased cell viability, migration, and colony formation. Conclusions This study revealed that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results suggest the promising potential of FOXO1 and PAX3 as prognostic and therapeutic markers. The possible link between biological functions of FOXO1 and PAX3 in EOC warrants further studies.

scholarly journals Prognostic implication of forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) in epithelial ovarian cancer.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 61-61
Author(s):  
Hanbyoul Cho ◽  
Gwan Hee Han ◽  
Jae-Hoon Kim
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Hazard Ratio ◽  
Ovarian Tumors ◽  
High Expression ◽  
Poor Grade ◽  
Epithelial Tissues ◽  
Forkhead Box ◽  
High Hazard Ratio

61 Background: Transcriptional factor, Forkhead box protein O1 (FOXO1) has been reported to play an imported role in human cancer, but the role in epithelial ovarian cancer (EOC) has not yet been clarified. Here, we evaluatedthe expression and clinical significance of FOXO1 in EOC. Methods: Immunohistochemical analyses of FOXO1 and PAX3 in 212 in EOCs, 57 borderline ovarian tumors and 153 benign epithelial ovarian tumors and 79 nonadjacent normal epithelial tissues were performed using tissue microarray analysis. The data were compared with clinicopathological variables including the survival of EOC patients. Also, the effect of FOXO1 on cell growth were assessed in EOC cell lines. Results: The expressions of FOXO1 and PAX3 protein were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues and borderline tumors respectively (all p< 0.001). Overexpression of FOXO1 was significantly associated with poor grade ( p = 0.004). FOXO1 expression showed trend of positive correlation with that of PAX3 in EOC tissues ( Spearman’s rho0.118, p= 0.149). Multivariate survival analysis revealed that the high expression of FOXO1 (hazard ratio = 2.74 [95% CI, 1.22–13.10], p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed high hazard ratio (hazard ratio = 5.53 [95% CI, 2.47–12.40], p< 0.001) for overall survival. In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability and migration. Conclusions: This study reveals that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results not only suggest the promising potential of FOXO1 and PAX3 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and PAX3 of EOC.

GENOMIC AND TRANSCRIPTOME PROFILING OF EPITHELIAL OVARIAN CANCER

2008 ◽  
Vol 31 (4) ◽  
pp. 17
Author(s):  
Rebecca JZ Menzies ◽  
Yury V Bukhman ◽  
Nancy F Ng ◽  
Patricia A Shaw ◽  
Tak W Mak
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Early Stage ◽  
Snp Array ◽  
Ovarian Tumors ◽  
Ca 125 ◽  
Molecular Heterogeneity ◽  
Presenting Symptoms

Background: Epithelial ovarian cancer is the leading cause of death by gynecological malignancy. Due to inadequate screening modalities, a lack of characteristic presenting symptoms, limited treatments and a poor understanding of the molecular underpinnings of the disease, only 25% of ovarian cancers are diagnosed at an early stage. Current 5-year survival rates range from 80%, for disease diagnosed in Stage I to as low as 13% for Stage IV. Current screening for ovarian cancer involves measuring CA-125 levels. However, CA-125 testing has low sensitivity since it can be elevated in a variety of other gynecological diseases. Numerous studies have found molecular heterogeneity between the four histological subtypes of ovarian cancer (serous, endometrioid, clear cell and mucinous). However, treatments remain the same for all subtypes regardless of molecular heterogeneity. Thus, better treatment targets and biomarkers must be found for this disease. Methods:In our study 300 ovarian tumors will be genomically profiled using the Affymetrix Genome-Wide SNP Array 6.0 to identify loci and genes implicated in ovarian cancer. To date, 51 ovarian tumors have been analyzed using the SNP array. Results:Preliminary analysis of copy number variation in these tumors using Partek software has revealed a total of 978 loci. Known amplifications derived from the literature were seen at CCNE1 and ERBB2. Similarly, well known deletions ofp53 and RB1 in ovarian cancer were detected. Novel amplified loci at 18q11.2 and 4q33 were also detected. Novel deletions were detected at 7p13 and 8q22.2. Conclusion: Future work will include running the remaining 249 tumor samples on the SNP array and analyzing the complete dataset using Partek software. Future validation of identified genes in vitro and in vivo may provide insight and possible biomarkers that may be used clinically to benefit the ovarian cancer patient.

scholarly journals The Role of Thrombocytosis as a Prognostic Factor for Epithelial Ovarian Cancer

2021 ◽  
pp. 153-156
Author(s):  
Andrijono ◽  
Heru Prasetyo ◽  
Eka R Gunardi ◽  
Gatot Purwoto ◽  
Hariyono Winarto
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Epithelial Ovarian Cancer ◽  
Cancer Registry ◽  
Hazard Ratio ◽  
Advanced Stage ◽  
Significant Difference ◽  
Mean Time

Objective: To determine whether thrombocytosis is a prognostic factor for epithelial ovarian cancer and its relationship with 3-year overall survival in epithelial ovarian cancer patients.Methods: This study is a retrospective cohort study using medical record of patients with epithelial ovarian cancer registered in cancer registry of Oncology Division in Obstetrics and Gynecology Department, Dr. Cipto Mangunkusumo National General Hospital from January 2014 - July 2016. Data were collected when subjects were first until diseases outcomes identified in 3 years.Results: : Out of 220 subjects, 132 (60%) were patients with advanced stage epithelial ovarian cancer (stage II/III/IV). 94 (42.7%) subjects had thrombocytosis. Patients with advanced stage of disease had higher risk of having thrombocytosis than the ones with earlier stage (p=0.005; OR=2.329). Correlation between thrombocytosis and 3-year overall survival was known to be insignificant (p=0.555). There was shorter mean time survival between patients with thrombocytosis and the ones without but the there was no significant difference in hazard ratio between the two groups (p  = 0.399).Conclusion :Thrombocytosis is not a prognostic factor in patients with epithelial ovarian cancer. There is also no significant difference of 3-year overall survival between patients with or without thrombocytosis.Keywords: epithelial ovarian carcinoma, prognosis,  thrombocytosis.   Abstrak Tujuan: Membuktikan bahwa trombositosis sebagai faktor prognosis kesintasan pada pasien kanker ovarium jenis epitelial dan hubungannya terhadap kesintasan 3 tahun pasien kanker ovarium  jenis epitelial.Metode: Penelitian ini merupakan studi kohort retrospektif menggunakan data rekam medis pasien kanker ovarium epitelial yang terdaftar pada cancer registry Departemen Obstetri dan Ginekologi Divisi Onkologi Rumah Sakit Cipto Mangunkusumo pada tahun Januari 2014-Juli 2016. Pengamatan dilakukan saat subjek pertama kali didiagnosis akhir pengamatan selama 3 tahun.Hasil: Didapatkan 220 subjek penelitian yang merupakan populasi terjangkau dan memenuhi kriteria inklusi dan eksklusi. Dari 220 subjek penelitian, 132 (60%) dari 220 subjek penelitian merupakan pasien dengan kanker ovarium stadium lanjut (Stadium II/III/IV). Trombositosis didapatkan pada 94 orang subjek penelitian (42,7%). Pasien dengan kanker stadium lanjut memiliki risiko trombositosis yang lebih tinggi dibandingkan subjek pada stadium awal (p=0,005;OR=2,329). Trombositosis secara statistik tidak bermakna pada kesintasan 3 tahun (p=0,555). Terdapat mean time survival yang lebih rendah pada pasien dengan trombositosis tetapi tidak ada perbedaan hazard ratio yang bermakna antara subjek dengan atau tanpa trombositosis (p=0,399).Kesimpulan : Trombositosis bukan merupakan faktor prognostik pada pasien kanker ovarium jenis epitelial dan tidak terdapat hubungan antara trombositosis dan 3 tahun pada pasien dengan kanker ovarium jenis epithelial.Kata kunci: karsinoma ovarium epithelial,  prognosis, trombositosis

scholarly journals Expression and prognostic significance of NKD2 in ovarian cancer

2020 ◽  
Author(s):  
Wei Wei ◽  
Lisi Zheng ◽  
Ying Gao ◽  
Minjun He ◽  
Fan Yang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Expression Profiles ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Negative Regulator ◽  
Free Survival

Abstract Purpose Naked2 (NKD2) is a negative regulator of Wnt signaling pathway and associates with transforming growth factor secretion. The role of NKD2 in ovarian cancer is unknown. Patients and methods Gene expression profiles were measured and compared in nine patients by RNA sequencing. NKD2 expressions in ovarian cancer were measured by reverse transcription polymerase chain reaction and western blot. Tissue slides of 79 patients were stained and scored for NKD2 expression. In vitro experiments were conducted to explore the role of NKD2 in ovarian cancer. The prognostic role of NKD2 was evaluated by survival analysis. Results NKD2 was upregulated in patients with better survival by mRNA and protein expression. Patients were classified as NKD2-high group (n = 30) and NKD2-low group (n = 49) according to immunohistochemical score. High NKD2 was correlated with lower recurrence rate (P = 0.002) and higher percentage of platinum-sensitive recurrence (P = 0.006). Median progression-free survival was significantly longer for NKD2-high patients than NKD2-low patients (49.1 vs.14.1 months, P &lt; 0.001). Accordingly, there was a significantly difference in terms of overall survival time between two groups (hazard ratio: 3.04; 95% confidence interval: 1.58–5.85, P &lt; 0.001). Multivariate regression suggested that NKD2 was independently prognostic factors in terms of progression-free survival (hazard ratio: 2.91; 95% confidence interval: 1.61–5.27, P &lt; 0.001) and overall survival (hazard ratio: 3.6; 95% confidence interval: 1.80–7.21, P &lt; 0.001). In vitro studies further demonstrated that NKD2 suppressed ovarian cancer cell proliferation, colony formation and cell migration. Conclusion NKD2 is a novel prognostic marker and could suppress tumor progression in ovarian cancer.

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

scholarly journals Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2489-2504 ◽  
Author(s):  
Le Chen ◽  
Ying Yao ◽  
Lijuan Sun ◽  
Jiajia Zhou ◽  
Minmin Miao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

scholarly journals Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients

2020 ◽  
Author(s):  
yu zhan ◽  
xueyuan wu ◽  
gang zheng ◽  
jingjing jin ◽  
chaofu li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Curative Surgery ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Prognostic Assessment ◽  
Therapy Strategies ◽  
Proline Rich Protein

Abstract Background: The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods: Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results: In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).Conclusions: The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

scholarly journals The forkhead box L2 transcription factor (FOXL2) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Ovarian Tumors ◽  
High Grade ◽  
Normal Ovary ◽  
Primary Tumors ◽  
Forkhead Box ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We identified the forkhead box L2, (FOXL2) (4) as among the genes whose expression was most different in HGSC ovarian tumors. FOXL2 expression was significantly lower in ovarian tumors relative to normal ovary. FOXL2 has established roles in ovarian development (4, 5), and the FOXL2 gene is mutated in granulosa-cell tumors of the ovary (6). These data indicate FOXL2 might also be perturbed, at the level of gene expression, in high-grade serous ovarian cancers.

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