A novel serum microRNA panel to discriminate benign from malignant ovarian disease (original) (raw)
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Circulating microRNA expression profiles in ovarian cancer
Journal of Obstetrics & Gynaecology, 2014
MicroRNA (miRNA) is an abundant class of small non-coding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about ovarian cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to fi nd specifi c profi les of plasmaderived miRNAs of ovarian cancer. In this present study, the expression profi les of 740 miRNAs in plasma from 18 patients and 24 healthy women subjects were evaluated using microfl uidic based multiplex qRT-PCR. Our results demonstrated that expression levels of 8 miRNAs were signifi cantly upregulated in patients with ovarian cancer when compared with a control group (p Ͻ 0.05). Expression levels of 4 miRNAs were found signifi cantly downregulated in patients with ovarian cancer (p Ͻ 0.05). In addition, 10 miRNAs were expressed only in the ovarian cancer group and miR-138-5p of these miRNAs is ovarian specifi c. In conclusion, our study suggests that detecting these ovarian cancer specifi c miRNAs in plasma might serve as novel non-invasive biomarkers for ovarian cancer.
MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer
Cancer biology & medicine, 2015
Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood sample...
The Potential of MicroRNAs as Clinical Biomarkers to Aid Ovarian Cancer Diagnosis and Treatment
Genes
Ovarian cancer is a commonly diagnosed malignancy in women. When diagnosed at an early stage, survival outcomes are favourable for the vast majority, with up to 90% of ovarian cancer patients being free of disease at 5 years follow-up. Unfortunately, ovarian cancer is typically diagnosed at an advanced stage due to the majority of patients remaining asymptomatic until the cancer has metastasised, resulting in poor outcomes for the majority. While the molecular era has facilitated the subclassification of the disease into distinct clinical subtypes, ovarian cancer remains managed and treated as a single disease entity. MicroRNAs (miRNAs) are small (19–25 nucleotides), endogenous molecules which are integral to regulating gene expression. Aberrant miRNA expression profiles have been described in several cancers, and have been implicated to be useful biomarkers which may aid cancer diagnostics and treatment. Several preliminary studies have identified candidate tumour suppressor and on...
microRNA as Biomarker in Ovarian Cancer Management: Advantages and Challenges
DNA and Cell Biology
Ovarian cancer is the most prevalent gynecological malignancy affecting women throughout the globe. Ovarian cancer has several subtypes, including epithelial ovarian cancer (EOC) with a whopping incidence rate of 239,000 per year, making it the sixth most common gynecological malignancy worldwide. Despite advancement of detection and therapeutics, death rate accounts for 152,000 per annum. Several protein-based biomarkers such as CA125 and HE4 are currently being used for diagnosis, but their sensitivity and specificity for early detection of ovarian cancer are under question. microRNA (a small noncoding RNA molecule that participates in posttranscription regulation of gene expression) and its functional deregulation in most cancers have been discovered in the previous two decades. Studies support that miRNA deregulation has an epigenetic component as well. Aberrant miRNA expression is often correlated with the form of EOC tumor, histological grade, prognosis, and FIGO stage. In this review, we addressed epigenetic regulation of miRNAs, the latest research on miRs as a biomarker in the detection of EOC, and tailored assays to use miRNAs as a biomarker in ovarian cancer diagnosis.
PLOS ONE, 2021
Advanced ovarian cancer is one of the most lethal gynecological tumor, mainly due to late diagnoses and acquired drug resistance. MicroRNAs (miRNAs) are small-non coding RNA acting as tumor suppressor/oncogenes differentially expressed in normal and epithelial ovarian cancer and has been recognized as a new class of tumor early detection biomarkers as they are released in blood fluids since tumor initiation process. Here, we evaluated by droplet digital PCR (ddPCR) circulating miRNAs in serum samples from healthy (N = 105) and untreated ovarian cancer patients (stages I to IV) (N = 72), grouped into a discovery/ training and clinical validation set with the goal to identify the best classifier allowing the discrimination between earlier ovarian tumors from health controls women. The selection of 45 candidate miRNAs to be evaluated in the discovery set was based on miRNAs represented in ovarian cancer explorative commercial panels. We found six miRNAs showing increased levels in the blood of early or late-stage ovarian cancer groups compared to healthy controls. The serum levels of miR-320b and miR-141-3p were considered independent markers of malignancy in a multivariate logistic regression analysis. These markers were used to train diagnostic classifiers comprising miRNAs (miR-320b and miR-141-3p) and miRNAs combined with well-established ovarian cancer protein markers (miR-320b, miR-141-3p, CA-125 and HE4). The miRNA-based classifier was able to accurately discriminate early-stage ovarian cancer patients from health-controls in an independent sample set (Sensitivity = 80.0%, Specificity = 70.3%, AUC = 0.789). In addition, the integration of the serum proteins in the model markedly improved the performance (Sensitivity = 88.9%, Specificity = 100%, AUC = 1.000). A cross-study validation was carried out using four data series obtained from Gene Expression Omnibus (GEO), corroborating the performance of the miRNA-based classifier (AUCs ranging from 0.637 to 0.979). The clinical utility of the miRNA model should be validated in a prospective cohort in order to investigate their feasibility as an ovarian cancer early detection tool.
Journal of Molecular and Genetic Medicine, 2018
MicroRNAs (miRNAs) are a special class of small non-coding RNAs that play a key role in gene regulations. In recent decades, many studies have suggested that miRNA deregulation is related to cancer development. Nevertheless, ovarian cancer (OC)-associated miRNA investigations are generally limited to tissue miRNA. In the present survey, we evaluated the specific profiles of serum-derived miRNAs of OC. The expression profiles of three miRNAs in the serum of the 31 OC and 28 healthy female subjects were examined by the Real-time-PCR technique. Our findings revealed that expression levels of the three examined miRNAs were significantly upregulated in OC subjects versus the control group (p<0.05). Indeed, miRNA146a, miRNA155, miRNA373 were overexpressed only in the OC group and these miRNAs seemed to be OC specific markers, which could be regulated by methylation and histone changes. In conclusion, the presented study proposed that the identification of these OC-specific miRNAs in serum might be considered as innovative non-invasive biomarkers.
Journal of Gynecologic Oncology
Objective: To correlate the genome-wide methylation signature of microRNA genes with dysregulated expression of selected candidate microRNA in tissue and serum samples of epithelial ovarian cancer (EOC) and control using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and evaluation of EOC predictive value of candidate microRNA at an early stage. Methods: We performed Methylated DNA Immunoprecipitation coupled with NGS (MeDIP-NGS) sequencing of 6 EOC and 2 normal tissue samples of the ovary. Expression of selected microRNA from tissue (EOC=85, normal=30) and serum (EOC=50, normal=15) samples was evaluated using qRT-PCR. We conducted bioinformatics analysis to identify the candidate miRNA's potential target and functional role. Results: MeDIP-NGS sequencing revealed hypermethylation of several microRNAs gene promoters. Three candidate microRNAs were selected (microRNA-34a, let-7f, and microRNA-31) from MeDIP-NGS data analysis based on log2FC and P-value. The relative expression level of microRNA-34a, let-7f, and microRNA-31 was found to be significantly reduced in early-stage EOC tissues and serum samples (p<0.0001). The receiver operating characteristic analysis of microRNA-34a, let-7f and miR-31 showed improved diagnostic value with area under curve(AUC) of 92.0 (p<0.0001), 87.9 (p<0.0001), and 85.6 (p<0.0001) and AUC of 82.7 (p<0.0001), 82.0 (p<0.0001), and 81.0 (p<0.0001) in stage III-IV and stage I-II EOC serum samples respectively. The integrated diagnostic performance of microRNA panel (microRNA-34a+let-7f+microRNA-31) in late-stage and early-stage serum samples was 95.5 and 96.9 respectively. Conclusion: Our data correlated hypermethylation-associated downregulation of microRNA in EOC. In addition, a combined microRNA panel from serum could predict the risk of EOC with greater AUC, sensitivity, and specificity.
MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features
World Journal of Surgical Oncology, 2012
Background: MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas. Methods: We measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis.
The circulating miRNA-34a, miRNA -143 and miRNA -212 are promising biomarkers in ovarian cancer
2022
Objective: Ovarian cancer is one of the most common gynaecological malignancies among females worldwide. Early diagnostic of ovarian cancer is challenging, and miRNAs could serve as a potential biomarker for early detection of ovarian cancer regarding easy to detect. The present study investigated the expression pro le of miRNA-34a, miRNA-143, miRNA-212, Sox4, BCL-2, and E2f5 in the serum of participants to nd new biomarkers for early diagnosis of ovarian cancer. Materials and Methods: Five milliliters of whole blood were collected from each patient (n=30) and control (n=30), and total RNA was extracted using Ambion™ TRIzol™ Reagent. Real-time PCR methods evaluated the expression of targeted miRNAs and their targeted genes. Result: The Disease status of all ovarian cancer patients were classi ed as FIGO stage III (21) and (IV 9) according to imaging studies and surgical pathological ndings. Our results showed that expression levels of miRNA-34a (p<0.0001), miRNA-143 (p=0.028), and miRNA-212 (p<0.0001) were signi cantly decreased in patients with ovarian cancer compared to controls and expression levels of Sox4(p<0.0001), BCL-2(p<0.0001) and E2f5(p<0.0001) were signi cantly increased in patients with ovarian cancer compared to controls. In addition, Receiver Operating Characteristic (ROC) curve revealed that the expression pro le of miRNA-34a (AUC= 0.82; P <0.0001), miRNA-143 (AUC= 0.66; P = 0.026) and miRNA-212 (AUC= 0.78; P = 0.0001) could be used as potential biomarker for discriminating patients with ovarian cancer. Conclusion: In conclusion, our data showed that the expression pro le of miRNA-34a, miRNA-143, and miRNA-212 could act as a potential biomarker for diagnosing ovarian cancer patients.
Role of microRNAs as Clinical Cancer Biomarkers for Ovarian Cancer: A Short Overview
Cells
Ovarian cancer has the highest mortality rate among gynecological cancers. Early clinical signs are missing and there is an urgent need to establish early diagnosis biomarkers. MicroRNAs are promising biomarkers in this respect. In this paper, we review the most recent advances regarding the alterations of microRNAs in ovarian cancer. We have briefly described the contribution of miRNAs in the mechanisms of ovarian cancer invasion, metastasis, and chemotherapy sensitivity. We have also summarized the alterations underwent by microRNAs in solid ovarian tumors, in animal models for ovarian cancer, and in various ovarian cancer cell lines as compared to previous reviews that were only focused the circulating microRNAs as biomarkers. In this context, we consider that the biomarker screening should not be limited to circulating microRNAs per se, but rather to the simultaneous detection of the same microRNA alteration in solid tumors, in order to understand the differences between the det...