scholarly journals Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Vivek Kumar ◽  
Sameer Gupta ◽  
Amrita Chaurasia ◽  
Manisha Sachan
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Ovarian Tissue ◽  
Characteristic Curve ◽  
Mirna Gene ◽  
Serum Samples ◽  
Cancer Management ◽  
Diagnostic Potential

BackgroundEpithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies among women worldwide. Early diagnosis of EOC could help in ovarian cancer management. MicroRNAs, a class of small non-coding RNA molecules, are known to be involved in post-transcriptional regulation of ~60% of human genes. Aberrantly expressed miRNAs associated with disease progression are confined in lipid or lipoprotein and secreted as extracellular miRNA in body fluid such as plasma, serum, and urine. MiRNAs are stably present in the circulation and recently have gained an importance to serve as a minimally invasive biomarker for early detection of epithelial ovarian cancer.MethodsGenome-wide methylation pattern of six EOC and two normal ovarian tissue samples revealed differential methylation regions of miRNA gene promoter through MeDIP-NGS sequencing. Based on log2FC and p-value, three hypomethylated miRNAs (miR-205, miR-200c, and miR-141) known to have a potential role in ovarian cancer progression were selected for expression analysis through qRT-PCR. The expression of selected miRNAs was analyzed in 115 tissue (85 EOC, 30 normal) and 65 matched serum (51 EOC and 14 normal) samples.ResultsAll three miRNAs (miR-205, miR-200c, and miR-141) showed significantly higher expression in both tissue and serum cohorts when compared with normal controls (p < 0.0001). The receiver operating characteristic curve analysis of miR-205, miR-200c, and miR-141 has area under the curve (AUC) values of 87.6 (p < 0.0001), 78.2 (p < 0.0001), and 86.0 (p < 0.0001), respectively; in advance-stage serum samples, however, ROC has AUC values of 88.1 (p < 0.0001), 78.9 (p < 0.0001), and 86.7 (p < 0.0001), respectively, in early-stage serum samples. The combined diagnostic potential of the three miRNAs in advance-stage serum samples and early-stage serum samples has AUC values of 95.9 (95% CI: 0.925–1.012; sensitivity = 96.6% and specificity = 80.0%) and 98.1 (95% CI: 0.941–1.021; sensitivity = 90.5% and specificity = 100%), respectively.ConclusionOur data correlate the epigenetic deregulation of the miRNA genes with their expression. In addition, the miRNA panel (miR-205 + miR-200c + miR-141) has a much higher AUC, sensitivity, and specificity to predict EOC at an early stage in both tissue and serum samples.

The Promising Signatures of Circulating microRNA-145 in Epithelial Ovarian Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Mariyam Zuberi ◽  
Rashid Mir ◽  
Imran Khan ◽  
Jamsheed Javid ◽  
Sameer Ahmad Guru ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Roc Curve ◽  
Histological Grade ◽  
Area Under The Curve ◽  
Lymph Node Status ◽  
P Value ◽  
Circulating Microrna ◽  
Serum Samples ◽  
Diagnostic Potential

Background:Epithelial ovarian cancer continues to be a deleterious threat to women as it is asymptomatic and is typically detected in advanced stages. Cogent non-invasive biomarkers are therefore needed which are effective in apprehending the disease in early stages. Recently, miRNA deregulation has shown a promising magnitude in ovarian cancer tumorigenesis. miRNA-145(miR- 145) is beginning to be understood for its possible role in cancer development and progression. In this study, we identified the clinicopathological hallmarks altered owing to the downexpression of serum miR-145 in EOC.Methods:70 serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-145 was detected by miRNA qRT-PCR using RNU6B snRNA as reference.Results:The alliance of miR-145 profiling amongst patients and controls established itself to be conspicuous with a significant p-value (p<0.0001). A positive conglomeration (p=0.04) of miR-145 profiling was manifested with histopathological grade. Receiver Operating Characteristic (ROC) curve highlights the diagnostic potential and makes it imminent with a robust Area Under the curve (AUC). A positive correlation with the ROC curve was also noted for histological grade, FIGO stage, distant metastasis, lymph node status and survival.Conclusion:Our results propose that miR-145 down-regulation might be a possible touchstone for disease progression and be identified as a diagnostic marker and predict disease outcome in EOC patients.

scholarly journals RETRACTED ARTICLE: Correlation of CD44v6 expression with ovarian cancer progression and recurrence

BMC Cancer ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Jun Shi ◽  
Zhou Zhou ◽  
Wen Di ◽  
Ningli Li
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Progression ◽  
Early Stage ◽  
Serous Adenocarcinoma ◽  
Potential Association ◽  
Skov3 Cells ◽  
Ovarian Serous Adenocarcinoma ◽  
And Migration ◽  
Cd44v6 Expression

Abstract Background Previously some groups demonstrated that CD44 variant 6 (CD44v6) is correlated with progression and metastasis of ovarian cancer. However, a number of other groups failed to find such an association. Moreover, epithelial ovarian cancer is known to easily metastasize to distinct sites such as the pelvic and abdominal cavities, but the potential association of CD44v6 expression with site-specific metastasis of ovarian cancer has not been explored. This study sought to evaluate the expression of CD44 standard (CD44s) and CD44v6 in primary, metastatic and recurrent epithelial ovarian cancer to explore the potential association of CD44s and CD44v6 with tumor progression and recurrence. Methods Tumor specimens were procured from patients with advanced (FIGO III, G3) and recurrent ovarian serous adenocarcinoma. CD44s and CD44v6 expression in the tumor tissues was evaluated by real-time RT-PCR and Western blot. Moreover, serum soluble CD44s or CD44v6 concentrations of early stage (FIGO I, G1), advanced (FIGO III, G3) and recurrent ovarian serous adenocarcinoma patients were determined by enzyme-linked immunosorbent assays (ELISA). CD44v6 expression in a different set of tumor samples on an ovarian cancer tissue chip was evaluated by immunohistochemistry (IHC) and the correlation of CD44v6 expression with clinicopathologic features was analyzed. Finally, the effects of knockdown of CD44v6 in SKOV3 cells on cell adhesion, invasion and migration were assessed. Results The expression of CD44v6, but not CD44s, is up-regulated in recurrent ovarian serous cancer compared to advanced primary tumor. CD44v6 expression is also preferentially increased in the tumor at the abdominal cavity metastasis site of advanced diseases. Consistently, serum soluble CD44v6 levels of recurrent ovarian cancer were higher than those of early stage and advanced primary diseases. The IHC data demonstrate that CD44v6 expression is correlated with clinicopathologic features and tumor progression. Lastly, knockdown of CD44v6 decreases the adhesion and migration but not invasion capacities of SKOV3 cells. Conclusions CD44v6 expression levels are associated with epithelial ovarian cancer progression, metastasis and relapse. Moreover, serum soluble CD44v6 may be used as a potential marker for identifying tumor relapse. Finally, CD44v6 may play a role in ovarian cancer metastasis by mediating tumor cell adhesion and migration.

scholarly journals Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Christopher Walker ◽  
Tuan-Minh Nguyen ◽  
Shlomit Jessel ◽  
Ayesha B. Alvero ◽  
Dan-Arin Silasi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Predictive Value ◽  
Early Stage ◽  
Ca 125 ◽  
Healthy Controls ◽  
Classification Models ◽  
Serum Samples ◽  
Protein Biomarker ◽  
Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

scholarly journals Does Time-to-Chemotherapy after Primary Complete Macroscopic Cytoreductive Surgery Influence Prognosis for Patients with Epithelial Ovarian Cancer? A Study of the FRANCOGYN Group

2021 ◽  
Vol 10 (5) ◽  
pp. 1058
Author(s):  
Grégoire Rocher ◽  
Thomas Gaillard ◽  
Catherine Uzan ◽  
Pierre Collinet ◽  
Pierre-Adrien Bolze ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Retrospective Cohort ◽  
Early Stage ◽  
Cohort Analysis ◽  
Recurrence Free Survival ◽  
Advanced Stage ◽  
Free Survival ◽  
Retrospective Cohort Analysis

To determine if the time-to-chemotherapy (TTC) after primary macroscopic complete cytoreductive surgery (CRS) influences recurrence-free survival (RFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC). We conducted an observational multicenter retrospective cohort analysis of women with EOC treated from September 2006 to November 2016 in nine institutions in France (FRANCOGYN research group) with maintained EOC databases. We included women with EOC (all FIGO stages) who underwent primary complete macroscopic CRS prior to platinum-based adjuvant chemotherapy. Two hundred thirty-three patients were included: 73 (31.3%) in the early-stage group (ESG) (FIGO I-II), and 160 (68.7%) in the advanced-stage group (ASG) (FIGO III-IV). Median TTC was 43 days (36–56). The median OS was 77.2 months (65.9–106.6). OS was lower in the ASG when TTC exceeded 8 weeks (70.5 vs. 59.3 months, p = 0.04). No impact on OS was found when TTC was below or above 6 weeks (78.5 and 66.8 months, respectively, p = 0.25). In the whole population, TTC had no impact on RFS or OS. None of the factors studied were associated with an increase in TTC. Chemotherapy should be initiated as soon as possible after CRS. A TTC greater than 8 weeks is associated with poorer OS in patients with advanced stage EOC.

Impact of guideline adherence on patient outcomes in early-stage epithelial ovarian cancer

2015 ◽  
Vol 41 (4) ◽  
pp. 585-591 ◽  
Author(s):  
J.-Y. Lee ◽  
T.H. Kim ◽  
D.H. Suh ◽  
J.W. Kim ◽  
H.S. Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Patient Outcomes ◽  
Guideline Adherence ◽  
Early Stage

scholarly journals Phosphatase Regenerating Liver3 and ECadherin Expression in Epithelial Ovarian Cancer

2017 ◽  
pp. 170-175
Author(s):  
Risma Maharani ◽  
Syahrul Rauf ◽  
Rina Masadah
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Early Stage ◽  
Cross Sectional Study ◽  
Teaching Hospitals ◽  
Advanced Stage ◽  
Cross Sectional ◽  
Exact Test ◽  
Significant Difference ◽  
E Cadherin

Objective: To determine the expression of Phosphatase Regenerating Liver-3 (PRL-3) and E-Cadherin in the epithelial ovarian cancer on various stages and differentiation grades. Method: This was a cross-sectional study design conducted at Obstetrics and Gynecology Department of several teaching hospitals, Faculty of Medicine Universitas Hasanuddin from January to June 2015. The expression of PRL-3 and E-cadherin was assessed immunohistochemically in 40 patients with epithelial ovarian cancer including 15 patients in early stage and 25 patients in advanced stage. We used the Fisher’s exact test with the significance of p0.05). The significant difference was found in the expression of E-cadherin whereas the high expression was shown at early stage than advanced stage (p0.05). This study also pointed out no correlation between the expression of PRL-3 and E-cadherin in epithelial ovarian cancer (p>0.05). Conclusion: PRL-3 overexpression does not decrease E-cadherin expression in epithelial ovarian cancer. Keywords: E-cadherin, epithelial ovarian cancer, PRL-3

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