Identification of a serum three-microRNA signature for cervical cancer diagnosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Cao MM
PROVIDER: S-EPMC8318658 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre-malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR-20a, miR-92a, miR-141, miR-183*, miR-210 and miR-944) were found to be significantly up-regulated in cervical cancer and pre-malignant lesions compared to normal cervical samples, indicating that they are oncogenic miRNAs. Receiver operating characteristic curve analysis showed that these six miRNAs can be used to distinguish patients with cervical pre-malignant lesions or cancer from normal individuals and they also had a good predictive performance, particularly in cervical lesions. Combined use of these six miRNAs further enhanced the diagnostic accuracy over any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959, a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%, 96.6% and 87.6% for low-grade lesions, high-grade lesions and cancer, respectively. This six oncogenic miRNA signature may be suitable for use as diagnostic marker for cervical pre-malignant lesions and cancer in the near future.
| S-EPMC6275249 | biostudies-literature
Project description:Dysregulated expression of specific microRNAs (miRNAs) in serum has been recognised as promising diagnostic biomarkers for colorectal cancer (CRC). In the initial screening phase, a total of 32 differentially expressed miRNAs were selected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel with 3 CRC pool samples and 1 normal control (NC) pool. Using qRT-PCR, selected serum miRNAs were further confirmed in training (30 CRC VS. 30 NCs) and testing stages (136 CRC VS. 90 NCs). We identified that serum levels of miR-19a-3p, miR-21-5p and miR-425-5p were significantly higher in patients with CRC than in NCs. The areas under the receiver operating characteristic (ROC) curve of the three-miRNA panel were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (30 CRC VS. 18 NCs), respectively. Significantly, elevated expression of the three miRNAs was also observed in CRC tissues (n = 24). Furthermore, the expression levels of the three miRNAs were significantly elevated in exosomes from CRC serum samples (n = 10). In conclusion, we identified a serum three-miRNA panel for the diagnosis of CRC.
| S-EPMC5370024 | biostudies-literature
Project description:Tumor cells that escape local tissue control can convert inflammatory cells from tumor suppressors to tumor promoters. Moreover, soluble immune-modulating factors secreted from the tumor environment can be difficult to identify in patient serum due to their low abundance. We used an alternative strategy to infer a metastatic signature induced by sera of cervical cancer patients.Sera from patients with local and metastatic cervical cancer were used to induce a disease-specific transcriptional signature in cultured, healthy peripheral blood mononuclear cells (PBMCs). An empirical Bayesian method, EBarrays, was used to identify differentially expressed (DE) genes with a target false discovery rate of <5%. Ingenuity Pathway Analysis (IPA) software was used to detect the top molecular and cellular functions associated with the DE genes. IPA and in silco analysis was used to pinpoint candidate upstream regulators, including cancer-related microRNAs (miRNAs).We identified enriched pathways in the metastatic cervical group related to immune surveillance functions, such as downregulation of engulfment, accumulation, and phagocytosis of hematopoietic cells. The predicted top upstream genes were IL-10 and immunoglobulins. In silco analysis identified miRNAs predicted to drive the transcriptional signature. Two of the 4 miRNAs (miR-23a-3p and miR-944) were validated in a cohort of women with local and metastatic cervical cancer.This study supports the use of a cell-based assay that uses PBMC "reporters" to predict biologically relevant factors in patient serum. Further, disease-specific transcriptional signatures induced by patient sera have the potential to differentiate patients with local versus metastatic disease.
| S-EPMC5576712 | biostudies-other
Project description:[This corrects the article DOI: 10.1371/journal.pone.0181242.].
| S-EPMC5825151 | biostudies-literature
Project description:Despite decades of efforts, non-small-cell lung cancer (NSCLC) remains the leading cause of cancer mortality globally primarily due to the challenge in early detection of the cancer. Being an important player in cancer development, the dysregulated miRNAs have been shown promising values as non-invasive diagnostic and prognostic biomarkers for NSCLC. The aim of our study is to access the efficacy and reliability of a potential circulating miRNA panel in early diagnosis of NSCLC. We first selected eight candidate miRNAs, miR-146b, miR-205, miR-29c, miR-31, miR-30b, miR-337, miR-411, and miR-708, which have been shown frequently aberrant in primary NSCLC patients based on our previous studies and other reports. The serum level of each of these miRNAs was evaluated by quantitative real-time PCR (qRT-PCR) in training and testing sets. We found that 5 out of 8 miRNAs (miR-146b, miR-205, miR-29c, miR-30b, and miR-337) were significantly up-regulated in NSCLCs patients compared to healthy or cancer-free controls in both training and testing sets. Based on the logistic regression model, a 4-miRNAs set (miR-146b, miR-205, miR-29c and miR-30b) was picked out of the 5 miRNAs owing to its excellent diagnostic power for NSCLC patients in the training set (AUC=0.99, accuracy=95.00%), the testing set (AUC=0.93, accuracy=89.69%), and the training-testing combined set ( AUC=0.96, accuracy=92.00%). When pathological subtypes of NSCLC are compared, this 4-miRNA panel carried a relatively higher prediction power and higher sensitivity for adenocarcinoma (AC) (AUC=0.98, sensitivity=99.10%) than for squamous cell carcinoma (SCC) (AUC=0.93, sensitivity=90.32%). Additionally, this panel demonstrated a comparable diagnostic capacity for stage I (AUC=0.96) and stage II-III (AUC=0.95) of NSCLC, suggesting its role in reflecting the tumor load. Importantly, the high levels of miR-146b and miR-29c in serum were significantly associated with poor 5-year overall survival (OS) (both p=0.04). Further survival analysis showed that high level of miR-146b in serum is specifically correlated with poor survival rate in SCC patients (p=0.0035) but not in AC patients (p=0.83), consistent with our previous finding that the high tissue expression of miR-146b in lung cancer specimen is indicative of a poor prognosis for SCC patients. Altogether, our study demonstrated that the 4-miRNA panel is a novel, sensitive and non-invasive serum marker for the early diagnosis of NSCLC.
| S-EPMC6643220 | biostudies-literature
Project description:Tumor cells that escape local tissue control can convert inflammatory cells from tumor suppressors to tumor promoters. Moreover, soluble immune-modulating factors secreted from the tumor environment can be difficult to identify in patient serum due to their low abundance. We used an alternative strategy,cell-based assay that uses PBMC “reporters” to predict biologically relevant factors in patient serum. We identified disease-specific transcriptional signatures induced by patient sera with local versus metastatic disease.
2017-07-01 | GSE100080 | GEO
Project description:Invasive cervical cancer is a leading cause of cancer death in women worldwide, resulting in about 300,000 deaths each year. The clinical outcomes of cervical cancer vary significantly and are difficult to predict. Thus, a method to reliably predict disease outcome would be important for individualized therapy by identifying patients with high risk of treatment failures before therapy. In this study, we have identified a microRNA (miRNA)-based signature for the prediction of cervical cancer survival. miRNAs are a newly identified family of small noncoding RNAs that are extensively involved in human cancers. Using an established PCR-based miRNA assay to analyze 102 cervical cancer samples, we identified miR-200a and miR-9 as two miRNAs that could predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with independent cervical cancers. Furthermore, functional studies were done to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by coordinate suppression of multiple genes controlling cell motility.
| S-EPMC2844247 | biostudies-literature
Project description:BackgroundDiagnosis of fibromyalgia (FM), a chronic musculoskeletal pain syndrome characterized by generalized body pain, hyperalgesia and other functional and emotional comorbidities, is a challenging process hindered by symptom heterogeneity and clinical overlap with other disorders. No objective diagnostic method exists at present. The aim of this study was to identify changes in miRNA expression profiles (miRNome) of these patients for the development of a quantitative diagnostic method of FM. In addition, knowledge of FM patient miRNomes should lead to a deeper understanding of the etiology and/or symptom severity of this complex disease.MethodsGenome-wide expression profiling of miRNAs was assessed in Peripheral Blood Mononuclear Cells (PBMCs) of FM patients (N=11) and population-age-matched controls (N=10) using human v16-miRbase 3D-Gene microarrays (Toray Industries, Japan). Selected miRNAs from the screen were further validated by RT-qPCR. Participating patients were long term sufferers (over 10 years) diagnosed by more than one specialist under 1990 American College of Rheumatology criteria.ResultsMicroarray analysis of FM patient PBMCs evidenced a marked downregulation of hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p, hsa-miR145-5p and hsa-miR-21-5p (4-fold or more). All but the mildest inhibited miRNA, hsa-miR-21-5p, were validated by RT-qPCR. Globally, 20% of the miRNAs analyzed (233/1212) showed downregulation of at least 2-fold in patients. This might indicate a general de-regulation of the miRNA synthetic pathway in FM. No significant correlations between miRNA inhibition and FM cardinal symptoms could be identified. However, the patient with the lowest score for mental fatigue coincided with the mildest inhibition in four of the five miRNAs associated with the FM-group.ConclusionsWe propose a signature of five strikingly downregulated miRNAs (hsa-miR223-3p, hsa-miR451a, hsa-miR338-3p, hsa-miR143-3p and hsa-miR145-5p) to be used as biomarkers of FM. Validation in larger study groups is required before the results can be transferred to the clinic.
| S-EPMC4372601 | biostudies-literature
Project description:Small non-coding microRNAs (miRNAs) are involved in cancer development and progression, and serum profiles of cervical cancer patients may be useful for identifying novel miRNAs. We performed deep sequencing on serum pools of cervical cancer patients and healthy controls with 3 replicates and constructed a small RNA library. We used MIREAP to predict novel miRNAs and identified 2 putative novel miRNAs between serum pools of cervical cancer patients and healthy controls after filtering out pseudo-pre-miRNAs using Triplet-SVM analysis. The 2 putative novel miRNAs were validated by real time PCR and were significantly decreased in cervical cancer patients compared with healthy controls. One novel miRNA had an area under curve (AUC) of 0.921 (95% CI: 0.883, 0.959) with a sensitivity of 85.7% and a specificity of 88.2% when discriminating between cervical cancer patients and healthy controls. Our results suggest that characterizing serum profiles of cervical cancers by Solexa sequencing may be a good method for identifying novel miRNAs and that the validated novel miRNAs described here may be cervical cancer-associated biomarkers.
| S-EPMC4152751 | biostudies-literature
Project description:We constructed a heterogeneous patient cohort of pre-treatment (prior to either surgery or chemotherapy) blood samples from 180 women enrolled in two independent prospective cohort studies of women presenting with an adnexal mass. One sample (E-1056) was later excluded due to an abnormally high level of mir-122 believed to be due to a recent MI. The remaining 179 samples were subdivided 3:1 into a 135 patient training set and 44 patient validation set. Total serum RNA was extracted, converted into miRNA next generation sequencing libraries, and sequenced. The variables for classification model development were selected using three methods – a significance filter (using a student’s t-test ), a group-stratified fold change filter, and a correlation-based feature selection (CFS). We deployed 11 different machine learning algorithms on the three sets of variables to separate the cases of invasive cancer from the healthy controls or benign/borderline masses. The tools were graded in terms of receiver operating characteristic area under the curve (ROC AUC). The model was validated both by qPCR on the study samples as well as by external validation on an independent publicly available dataset of 454 patients with a range of diagnoses, including ovarian cancer. The qPCR signature was then externally validated on another independent external cohort.
2017-10-13 | GSE94533 | GEO