scholarly journals Non-coding Somatic Mutations Converge on the PAX8 Pathway in Epithelial Ovarian Cancer

2019 ◽  
Author(s):  
Rosario I. Corona ◽  
Ji-Heui Seo ◽  
Xianzhi Lin ◽  
Dennis J. Hazelett ◽  
Jessica Reddy ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Target Genes ◽  
Clear Cell ◽  
Regulatory Elements ◽  
Integrated Analysis ◽  
Single Nucleotide Variants ◽  
Primary Tumors ◽  
Invasive Epithelial Ovarian Cancer ◽  
Functional Analyses

ABSTRACTTranscriptional regulation is highly disease and cell-type specific. We performed H3K27ac chromatin immunoprecipitation and transcriptomic sequencing in primary tumors for the four different subtypes of invasive epithelial ovarian cancer (OC). Histotype-specific regulatory elements (REs) were enriched in enhancers (P<0.001).In silicoprediction of putative target genes for histotype-specific REs identified genes (WFDC2, P=5.5×10-5) and pathways (PI3K-Akt signaling, P<0.002) known to be involved in OC development. Some genes (e.g.PAX8andCA125) are associated with super-enhancers (SEs) in all OCs, while others are histotype-specific, includingPPP1R3Bwhich is associated with SEs specific to clear cell OC. Integrated analysis of active chromatin landscapes with somatic single nucleotide variants (SNVs) from whole genome sequencing (WGS) of 232 primary OCs identified frequently mutated REs, including theKLF6promoter (P=8.2×10-8) and a putative enhancer at chromosome 6p22.1 (P<0.05). In high-grade serous OCs, somatic SNVs clustered in binding sites for the PAX8 binding partner TEAD4 (P=6×10-11), while the collection ofcisregulatory elements associated withPAX8was the most frequently mutated set of enhancers in OC (P=0.003). Functional analyses supported our findings: Knockdown ofPPP1R3Bin clear cell OC cells significantly reduced intracellular glycogen content, a signature feature of this histotype; and stable knockout of a 635 bp region in the 6p22.1 enhancer induced downregulation of two predicted target genes,ZSCAN16andZSCAN12(P=6.6 x 10-4and P=0.02). In summary, we have characterized histotype-specific epigenomic and transcriptomic landscapes in OC and defined likely functional REs based on somatic mutation analysis of ovarian tumors.

A loss of microRNA expression as a characterization of synchronous peritoneal secondary localizations of epithelial ovarian cancer as compared to primary tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11037-11037
Author(s):  
Delia Mezzanzanica ◽  
Loris De Cecco ◽  
Daniela Califano ◽  
Simona Losito ◽  
Marina Bagnoli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Target Genes ◽  
Ectopic Expression ◽  
Differentially Expressed ◽  
Platinum Resistance ◽  
Primary Tumors ◽  
Gynecological Malignancy ◽  
Primary Surgery

11037 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy and one of the most challenging areas of cancer research being a highly heterogeneous disease difficult to diagnose and treat. EOC has a peculiar dissemination process due to the sloughing-off of cells from primary tumors and their spread throughout the peritoneal cavity. A better characterization of the mechanism involved in tumor spreading might help in design new therapeutic intervention. Methods: Forty-four couples of chemo naïf primary tumors and synchronous secondary peritoneal localizations, obtained at primary surgery from MITO2 clinical trial, have been profiled for microRNA (miRNA) expression on an Agilent Platform. Total RNA was extracted from formalin-fixed paraffin embedded tissues. An independent validation set of samples with similar characteristics, has been collected at INT Milan. Results: By class comparison analysis, imposing a false discovery rate <10%,45 miRNAs were identified as differentially expressed: 32 down-modulated and 13 up-modulated in secondary localizations compared to primary tumors. Among the miRNAs down-modulated in the secondary localizations we detected most of the miRNA belonging to the Xq27.3 cluster, whose low expression we previously described to be associated with EOC early relapse, and a number of miRNAs related to epithelial/mesenchimal transition (EMT) whose modulation could be related to dissemination of the disease and response to drug treatment. In particularly loss of has-miR-506 resulted associated to platinum resistance since its ectopic expression in EOC cell lines increased their sensitivity to the drug. Furthermore preliminary data indicated that has-miR-506 regulated N-cadherin linking its modulation to EMT. Conclusions: To our knowledge, the present study is the first attempt to characterize a miRNA signature differentially expressed between EOC primary tumors and synchronous secondary peritoneal localizations. The validation of the miRNA profile as well as of target genes might help in elucidating EOC dissemination mechanisms and in defining possible new therapeutic targets.

scholarly journals Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

2020 ◽  
Author(s):  
Alice W Lee ◽  
Stacey Rosenzweig ◽  
Ashley Wiensch ◽  
Susan J Ramus ◽  
Usha Menon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Epithelial Ovarian Cancer ◽  
Race And Ethnicity ◽  
Clear Cell ◽  
Ovarian Cancer Risk ◽  
Inverse Association ◽  
Case Control Studies ◽  
Invasive Epithelial Ovarian Cancer ◽  
Reduced Risk

Abstract Background Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend &lt; .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

scholarly journals Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1839
Author(s):  
Karolina Seborova ◽  
Radka Vaclavikova ◽  
Lukas Rob ◽  
Pavel Soucek ◽  
Pavel Vodicka
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distant Metastases ◽  
Regulatory Elements ◽  
Metastatic Spread ◽  
Response To Treatment ◽  
Primary Tumors ◽  
Non Coding Rnas

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

scholarly journals MiR-200c-3p Contrasts PD-L1 Induction by Combinatorial Therapies and Slows Proliferation of Epithelial Ovarian Cancer through Downregulation of β-Catenin and c-Myc

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 519
Author(s):  
Eleni Anastasiadou ◽  
Elena Messina ◽  
Tiziana Sanavia ◽  
Lucia Mundo ◽  
Federica Farinella ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Ovarian Cancer Cells ◽  
Oncogenic Signaling ◽  
Experimental Conditions ◽  
Skov3 Cells ◽  
In Silico Analyses ◽  
Post Therapy

Conventional/targeted chemotherapies and ionizing radiation (IR) are being used both as monotherapies and in combination for the treatment of epithelial ovarian cancer (EOC). Several studies show that these therapies might favor oncogenic signaling and impede anti-tumor responses. MiR-200c is considered a master regulator of EOC-related oncogenes. In this study, we sought to investigate if chemotherapy and IR could influence the expression of miR-200c-3p and its target genes, like the immune checkpoint PD-L1 and other oncogenes in a cohort of EOC patients’ biopsies. Indeed, PD-L1 expression was induced, while miR-200c-3p was significantly reduced in these biopsies post-therapy. The effect of miR-200c-3p target genes was assessed in miR-200c transfected SKOV3 cells untreated and treated with olaparib and IR alone. Under all experimental conditions, miR-200c-3p concomitantly reduced PD-L1, c-Myc and β-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c-3p with c-Myc and β-catenin in 46 OC cell lines and showed that a higher miR-200c-3p expression associates with a less tumorigenic microenvironment. These findings provide new insights into how miR-200c-3p could be used to hold in check the adverse effects of conventional chemotherapy, targeted therapy and radiation therapy, and offer a novel therapeutic strategy for EOC.

Outcome of Reproductive Age Women With Stage IA or IC Invasive Epithelial Ovarian Cancer Treated With Fertility-Sparing Therapy

2003 ◽  
Vol 58 (4) ◽  
pp. 254-255
Author(s):  
Jeanne M. Schilder ◽  
Amy M. Thompson ◽  
Paul D. DePriest ◽  
Frederick R. Ueland ◽  
Michael L. Cibull ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Reproductive Age ◽  
Reproductive Age Women ◽  
Fertility Sparing ◽  
Stage Ia ◽  
Invasive Epithelial Ovarian Cancer

Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs

2007 ◽  
Vol 38 (1) ◽  
pp. 134-139 ◽  
Author(s):  
Sadako Nishimura ◽  
Hiroshi Tsuda ◽  
Kiyoshi Ito ◽  
Toshiko Jobo ◽  
Nobuo Yaegashi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Differential Expression ◽  
Clear Cell ◽  
Histologic Types

scholarly journals Survival of Australian women with invasive epithelial ovarian cancer: a population‐based study

2014 ◽  
Vol 201 (5) ◽  
pp. 283-288 ◽  
Author(s):  
Satyamurthy Anuradha ◽  
Penelope M Webb ◽  
Penny Blomfield ◽  
Alison H Brand ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Population Based ◽  
Population Based Study ◽  
Invasive Epithelial Ovarian Cancer

scholarly journals Differential expression of SLIT and NTRK-like family member 3 in human epithelial ovarian cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Family Member ◽  
Fallopian Tube ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
High Grade ◽  
Primary Tumors ◽  
Ovarian Cancers

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published and public microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding SLIT and NTRK-like family member 3, SLITRK3, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. SLITRK3 expression was significantly lower in high-grade serous ovarian tumors relative to normal fallopian tube. SLITRK3 expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of SLITRK3 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. SLITRK3 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

scholarly journals Differential expression of LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated in human epithelial ovarian cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Fallopian Tube ◽  
Expression Profiles ◽  
Mrna Degradation ◽  
High Grade ◽  
Small Nuclear Rna ◽  
Primary Tumors ◽  
Ovarian Cancers ◽  
Nuclear Rna

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated, LSM4, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. LSM4 expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. LSM4 expression correlated with overall survival in patients with ovarian cancer. These data indicate that expression of LSM4 is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. LSM4 may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

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