scholarly journals ZYG11A Is Expressed in Epithelial Ovarian Cancer and Correlates With Low Grade Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Laris Achlaug ◽  
Lina Somri-Gannam ◽  
Shilhav Meisel-Sharon ◽  
Rive Sarfstein ◽  
Manisha Dixit ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Growth Hormone Receptor ◽  
Histological Grade ◽  
Inverse Correlation ◽  
Low Grade ◽  
Mrna Levels ◽  
Knock Out ◽  
Coordinated Expression ◽  
Candidate Target

The insulin-like growth factors (IGF) are important players in the development of gynecological malignancies, including epithelial ovarian cancer (EOC). The identification of biomarkers that can help in the diagnosis and scoring of EOC patients is of fundamental importance in clinical oncology. We have recently identified the ZYG11A gene as a new candidate target of IGF1 action. The aim of the present study was to evaluate the expression of ZYG11A in EOC patients and to correlate its pattern of expression with histological grade and pathological stage. Furthermore, and in view of previous analyses showing an interplay between ZYG11A, p53 and the IGF1 receptor (IGF1R), we assessed a potential coordinated expression of these proteins in EOC. In addition, zyg11a expression was assessed in ovaries and uteri of growth hormone receptor (GHR) knock-out mice. Tissue microarray analysis was conducted on 36 patients with EOC and expression of ZYG11A, IGF1R and p53 was assessed by immunohistochemistry. Expression levels were correlated with clinical parameters. qPCR was employed to assess zyg11a mRNA levels in mice tissues. Our analyses provide evidence of reduced ZYG11A expression in high grade tumors, consistent with a putative tumor suppressor role. In addition, an inverse correlation between ZYG11A and p53 levels in individual tumors was noticed. Taken together, our data justify further exploration of the role of ZYG11A as a novel biomarker in EOC.

scholarly journals Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1917 ◽  
Author(s):  
Changwon Yang ◽  
Hee Seung Kim ◽  
Soo Jin Park ◽  
Eun Ji Lee ◽  
Se Ik Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Target Genes ◽  
Apoptotic Cell ◽  
Serous Cystadenoma ◽  
Low Grade ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Potential Biomarker ◽  
Platinum Based Chemotherapy

In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, p < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.

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.

Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer

2016 ◽  
pp. e247-e257 ◽  
Author(s):  
Keiichi Fujiwara ◽  
Jessica N. McAlpine ◽  
Stephanie Lheureux ◽  
Noriomi Matsumura ◽  
Amit M. Oza
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Paradigm Shift ◽  
Management Strategy ◽  
Clear Cell ◽  
Treatment Strategies ◽  
Low Grade ◽  
Ovarian Carcinomas ◽  
Coelomic Epithelium ◽  
Histologic Types

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

scholarly journals Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1554
Author(s):  
Enrica Calura ◽  
Matteo Ciciani ◽  
Andrea Sambugaro ◽  
Lara Paracchini ◽  
Giuseppe Benvenuto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Stage I ◽  
Molecular Heterogeneity ◽  
Low Grade ◽  
Multicentric Study ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Signaling Axis ◽  
Tumor Biopsies

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

Circulating tumor DNA analysis to reveal genomic profiles for epithelial ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5543-5543
Author(s):  
Yang Xiang ◽  
Shan Zhu ◽  
Weiran Wang ◽  
Dongyan Cao ◽  
Xi-Run Wan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Epithelial Ovarian Cancer ◽  
Circulating Tumor Dna ◽  
Stage Iii ◽  
Signal Pathways ◽  
Low Grade ◽  
Serous Ovarian Carcinoma ◽  
Ctdna Analysis ◽  
Tumor Dna

5543 Background: Circulating tumor DNA (ctDNA) analysis in epithelial ovarian cancer (EOC) was previously reported, however with limited samples or limited genes. Here, we reported an analysis of ctDNA in EOC cohort using targeted sequencing with a 1021-gene panel. Methods: Patients with EOC were enrolled, and treatment-naïve tumor tissues and blood samples were collected. We utilized a 1021-gene NGS panel in matched tissue DNA and ctDNA to identify somatic mutations with white blood cell DNA as a germline control. Results: Mutations were identified in all of the 65 tissues and in 53 (81.5%) ctDNA. The median ctDNA mutation allelic frequency was 2.5%, ranging from 0.1% to 36.2%. A median of 66.7% (12.5%-100.0%) of tissue derived mutations were observed in ctDNA. Besides, there were 91 ctDNA private mutations, including TP53 gene mutations. The most frequently mutated genes were TP53 (55.4%), PIK3CA (13.8%) and ARID1A (12.3%) in ctDNA analysis, which were consistent with tissue analysis (60.0%, 26.2% and 20.0% of tissues with TP53, PIK3CA and ARID1A mutations, respectively). Mutations of TP53 (37/42) in high-grade serous ovarian carcinoma (HGSOC), PIK3CA (10/11) and ARID1A (8/11) in ovarian clear cell carcinoma, BRAF (4/5) in low-grade serous ovarian carcinoma and PIK3CA (3/5), ARID1A (2/5) and PTEN (2/5) in endometrioid carcinoma were observed as the most commonly genetic aberrations in ctDNA in different sub-types of EOC, which located in different signal pathways and suggested different pathogenesis. In total, 90.5% (38/42) of HGSOC were ctDNA positive, comparing with 65.2% (15/23) of other EOC subtypes (p = 0.012). In addition, 56.5% (13/23) of stage I~II EOC were ctDNA positive, comparing with 94.7% (36/38) of stage III (p = 0.002). No association between ctDNA positivity and other clinic characteristics was observed, including pathological differentiation, CA125, lesion density (solid vs. cystic-solid and cystic). Multivariable analysis suggested FIGO stage III (p = 0.008) as an independent predictor of ctDNA detection. Conclusions: In summary, genomic characterization of EOC may offer insights into tumorigenesis and identify potential therapeutic targets in this disease.

Low-grade epithelial ovarian cancer

2015 ◽  
Vol 27 (5) ◽  
pp. 412-419 ◽  
Author(s):  
Ailsa J. Oswald ◽  
Charlie Gourley
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Low Grade

scholarly journals Systematic Lymph Node Dissection May Be Abolished in Patients With Apparent Early-Stage Low-Grade Mucinous and Endometrioid Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiayu Chen ◽  
Jie Yin ◽  
Yan Li ◽  
Yu Gu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Epithelial Ovarian Cancer ◽  
Lymph Node Dissection ◽  
Early Stage ◽  
Progression Free Survival ◽  
Low Grade ◽  
Node Dissection ◽  
Surgical Methods ◽  
Systematic Lymph Node Dissection

ObjectiveTo investigate whether systematic lymph node dissection can confer clinical benefits in patients with apparent early-stage low-grade epithelial ovarian cancer.MethodsPatients with apparent early-stage low-grade epithelial ovarian cancer seen at Peking Union Medical College Hospital from January 1, 2005, to December 31, 2015, were retrospectively enrolled. Patients with other histological types and those who did not receive necessary adjuvant chemotherapy were excluded. Data collection and long-term follow-up were performed. According to the removed lymph node number, three groups based on surgical methods were used: abnormal lymph node resection, pelvic lymphadenectomy, and systematic lymph node dissection to control surgical quality. Their effects on prognosis were analyzed in pathological subgroups.ResultsA total of 196 patients were enrolled; 30.1% of patients had serous, 42.3% of patients had mucinous, and 27.6% of patients had endometrioid carcinoma, of which 51 (26.0%), 96 (49.0), and 49 (25.0%) patients were treated with the above surgical methods, respectively. The occult lymph node metastasis rate was 14 (7.1%), and only five (2.6%) of apparent early-stage patients were upstaged due to lymph node metastasis alone. Systematic lymph node dissection did not benefit progression-free survival or disease-specific overall survival of apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but prolonged progression-free survival of apparent early-stage low-grade serous patients (OR, 0.231, 95% CI, 0.080, 0.668, p = 0.007).ConclusionsSystematic lymph node dissection may be abolished in patients with apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but may be considered for apparent early-stage low-grade serous patients.

Sign in / Sign up

Export Citation Format

Share Document