scholarly journals Circulating Exosomal miRNAs as Biomarkers in Epithelial Ovarian Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1433
Author(s):  
Meng-Shin Shiao ◽  
Jia-Ming Chang ◽  
Arb-Aroon Lertkhachonsuk ◽  
Naparat Rermluk ◽  
Natini Jinawath
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Epithelial Ovarian Cancer ◽  
Early Stage ◽  
Cell Communication ◽  
Biological Molecules ◽  
Non Invasive ◽  
Exosomal Mirnas ◽  
Endogenous Reference ◽  
Treatment Responses

Failure to detect early-stage epithelial ovarian cancer (EOC) is a major contributing factor to its low survival rate. Increasing evidence suggests that different subtypes of EOC may behave as distinct diseases due to their different cells of origins, histology and treatment responses. Therefore, the identification of EOC subtype-specific biomarkers that can early detect the disease should be clinically beneficial. Exosomes are extracellular vesicles secreted by different types of cells and carry biological molecules, which play important roles in cell-cell communication and regulation of various biological processes. Multiple studies have proposed that exosomal miRNAs present in the circulation are good biomarkers for non-invasive early detection of cancer. In this review, the potential use of exosomal miRNAs as early detection biomarkers for EOCs and their accuracy are discussed. We also review the differential expression of circulating exosomal miRNAs and cell-free miRNAs between different biofluid sources, i.e., plasma and serum, and touch on the issue of endogenous reference miRNA selection. Additionally, the current clinical trials using miRNAs for detecting EOCs are summarized. In conclusion, circulating exosomal miRNAs as the non-invasive biomarkers have a high potential for early detection of EOC and its subtypes, and are likely to be clinically important in the future.

scholarly journals Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingjing Liu ◽  
Jigeun Yoo ◽  
Jung Yoon Ho ◽  
Yuyeon Jung ◽  
Sanha Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Healthy Subjects ◽  
Early Stage ◽  
Roc Curves ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Potential Biomarker ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Abstract Background Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC). Methods In total, 55 individuals were enrolled, comprising healthy (n = 21) and EOC subjects (n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity. Results Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p<0.0001) and could be a potential biomarker for monitoring the EOC progression from early stage to late stage (p = 0.018). Conclusions Plasma derived exosomal miR-4732-5p may be a promising candidate biomarker for diagnosing EOC.

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 Multianalyte Tests for the Early Detection of Cancer: Speedbumps and Barriers

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Michael A. Tainsky ◽  
Madhumita Chatterjee ◽  
Nancy K. Levin ◽  
Sorin Draghici ◽  
Judith Abrams
Keyword(s):  
Early Detection ◽  
Tumor Antigens ◽  
Early Stage ◽  
False Negative ◽  
Clinical Intervention ◽  
Screening Tests ◽  
Molecular Event ◽  
Non Invasive ◽  
In Vitro Diagnostic

It has become very clear that a single molecular event is inadequate to accurately predict the biology (or pathophysiology) of cancer. Furthermore, using any single molecular event as a biomarker for the early detection of malignancy may not comprehensively identify the majority of individuals with that disease. Therefore, the fact that technologies have arisen that can simultaneously detect several, possibly hundreds, of biomarkers has propelled the field towards the development of multianalyte-based in vitro diagnostic early detection tests for cancer using body fluids such as serum, plasma, sputum, saliva, or urine. These multianalyte tests may be based on the detection of serum autoantibodies to tumor antigens, the presence of cancer-related proteins in serum, or the presence of tumor-specific genomic changes that appear in plasma as free DNA. The implementation of non-invasive diagnostic approaches to detect early stage cancer may provide the physician with evidence of cancer, but the question arises as to how the information will affect the pathway of clinical intervention. The confirmation of a positive result from an in vitro diagnostic cancer test may involve relatively invasive procedures to establish a true cancer diagnosis. If in vitro diagnostic tests are proven to be both specific, i.e. rarely produce false positive results due to unrelated conditions, and sufficiently sensitive, i.e. rarely produce false negative results, then such screening tests offer the potential for early detection and personalized therapeutics using multiple disease-related targets with convenient and non-invasive means. Here we discuss the technical and regulatory barriers inherent in development of clinical multianalyte biomarker assays.

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