Diagnostic value of oncofetal miRNAs in cancers: A comprehensive analysis of circulating miRNAs in pan-cancers and UCB

2021 ◽  
pp. 1-18
Author(s):  
Xin Zhou ◽  
Cheng Liu ◽  
Yin Yin ◽  
Cheng Zhang ◽  
Xuan Zou ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Diagnostic Value ◽  
Comprehensive Analysis ◽  
Detection Methods ◽  
Plasma Samples ◽  
Circulating Mirnas ◽  
Serum Samples ◽  
Chinese Populations ◽  
Non Invasive ◽  
Plasma Mirnas

BACKGROUND: Circulating miRNAs are promising biomarkers for detection of various cancers. As a “developmental” disorder, cancer showed great similarities with embryos. OBJECTIVE: A comprehensive analysis of circulating miRNAs in umbilical cord blood (UCB) and pan-cancers was conducted to identify circulating miRNAs with potential for cancer detection. METHODS: A total of 3831 cancer samples (2050 serum samples from 15 types of cancers and 1781 plasma samples from 13 types of cancers) and 248 UCB samples (120 serum and 128 plasma samples) with corresponding NCs from Chinese populations were analyzed via consistent experiment workflow with Exiqon panel followed by multiple-stage validation with qRT-PCR. RESULTS: Thirty-four serum and 32 plasma miRNAs were dysregulated in at least one type of cancer. Eighteen serum and 16 plasma miRNAs were related with embryos. Among them, 9 serum and 8 plasma miRNAs with consistent expression patterns between pan-cancers and UCB were identified as circulating oncofetal miRNAs. Retrospective analysis confirmed the diagnostic ability of circulating oncofetal miRNAs for specific cancers. And the oncofetal miRNAs were mainly up-regulated in tissues of pan-cancers. CONCLUSIONS: Our study might serve as bases for the potential application of the non-invasive biomarkers in the future clinical.

scholarly journals Experimental Validation of a Potential Circulating microRNA Panel for Non-Invasive Pancreatic Cancer Diagnosis

2021 ◽  
Author(s):  
Ali Seyed Salehi ◽  
Negar Parsa ◽  
Farnaz Roshan-Farzad ◽  
Ali Behmanesh ◽  
Mohadeseh Fathi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Differential Expression Analysis ◽  
External Validation ◽  
Diagnostic Value ◽  
Ductal Adenocarcinoma ◽  
Circulating Microrna ◽  
Plasma Samples ◽  
Serum Samples ◽  
Non Invasive ◽  
Testing Stage

Abstract MicroRNA (miRNA) expression dysregulations in pancreatic ductal adenocarcinoma (PDAC) have been studied widely for their diagnostic and prognostic utility. By the use of Bioinformatics-based methods, in our previous study, we identified some potential miRNA panels for diagnosis of Pancreatic cancer patients from non-cancerous controls (the screening stage). In this report, we used 142 plasma samples from people with and without pancreatic cancer (PC) to conduct RT-qPCR differential expression analysis to assess the strength of the first previously proposed diagnostic panel (consisting of miR-125a-3p, miR-4530 and miR-92a-2-5p). For this aim the research was divided into two phases: testing, and external validation. A total of 92 PC plasma samples and normal controls (NCs) were evaluated in the testing stage to determine the ability of the considered miRNAs to discriminate cancer from non-cancer samples as a panel. Furthermore, in the external validation phase, a group of 25 PC serum samples vs. 25 NCs was employed to validate the diagnostic value of the panel. As the result, we identified significant up-regulation for all the three considered miRNAs in the serum of PC patients. After that, a three-miRNA panel in serum was developed. For the testing, validating and combined stages, the area under the receiver operating characteristic curves (AUC) for the panel were 0.850, 0.910 and 0.86 respectively, indicating that it had a higher diagnostic value than individual miRNAs. Therefore, we detected a promising three-miRNA panel in the plasma for non-invasive PC diagnosis (miR-125a-3p, miR-4530 and miR-92a-2-5p).

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer

2021 ◽  
pp. 1-12
Author(s):  
Xingchen Fan ◽  
Minmin Cao ◽  
Cheng Liu ◽  
Cheng Zhang ◽  
Chunyu Li ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
External Validation ◽  
Diagnostic Value ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Polymerase Chain ◽  
Public Datasets ◽  
Plasma Mirnas

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

Circulating miR-126 as a Potential Non-invasive Biomarker for Intracranial Aneurysmal Rupture: A Pilot Study

2021 ◽  
Vol 19 ◽  
Author(s):  
Jianing Wu ◽  
Ilgiz Gareev ◽  
Ozal Beylerli ◽  
Albert Mukhamedzyanov ◽  
Valentin Pavlov ◽  
...  
Keyword(s):  
Aneurysmal Subarachnoid Hemorrhage ◽  
Diagnostic Value ◽  
Plasma Samples ◽  
Expression Levels ◽  
Time Points ◽  
Non Invasive ◽  
Risk Of Rupture ◽  
Life Threatening ◽  
Healthy Control ◽  
New Biomarkers

Aim: Intracranial aneurysms (IAs) are characterized by abnormal dilation and thinning of the cerebral vessels wall, leading to rupture and life-threatening aneurysmal subarachnoid hemorrhage (aSAH) condition. This dictates the need to find new biomarkers that predict the presence of IAs and the risk of their rupture. The aim of this study was to measure circulating miR-126 at various time points post-aSAH to identify the timing of peak levels. Methods: Plasma samples from 62 patients with unruptured IAs (UIAs), 80 patients with aSAH at various time points (1, 3, 7, and 14 days post-event), and 47 healthy control were collected and subjected to qRT-PCR analyses for the expression levels of circulating miR-126. ROC curve and AUC were used to evaluate the diagnostic value of circulating miR-126. Results: The expression levels of circulating miR-126 were increased in patients with UIAs than in the healthy control. Furthermore, the expression levels of circulating miR-126 rose substantially from day 1 to day 7, but with a moderate decrease from day 7 to day 14 in plasma of patients with aSAH. The peak was observed on day 7. The AUC for miR-126 was 0.75, 0.75, 0.82, 0.87, and 0.79, respectively, and demonstrated that circulating miR-126 displayed considerable accuracy in discriminating plasma of patients with UIAs and patients after aSAH at various time points from a healthy control. Conclusion: Our results indicated that circulating miR-126 in plasma samples could be served as a potential non-invasive biomarker in IAs detection and prevention IAs with a high risk of rupture.

scholarly journals Increased Expression of Plasma miRNA-320a and let-7b-5p in Heroin-Dependent Patients and Its Clinical Significance

2021 ◽  
Vol 12 ◽  
Author(s):  
Haixiong Liu ◽  
Wenjin Xu ◽  
Jiying Feng ◽  
Hong Ma ◽  
Jianbin Zhang ◽  
...  
Keyword(s):  
Roc Curves ◽  
Brain Diseases ◽  
Circulating Mirnas ◽  
Heroin Use ◽  
Non Invasive ◽  
Heroin Use Disorder ◽  
Subjective Reports ◽  
The Brain ◽  
Potential Use ◽  
Plasma Mirnas

Heroin use disorder is a chronic and relapsing disease that induces persistent changes in the brain. The diagnoses of heroin use disorders are mainly based on subjective reports and no valid biomarkers available. Recent researches have revealed that circulating miRNAs are useful non-invasive biomarkers for diagnosing brain diseases such as Alzheimer's disease, multiple sclerosis, schizophrenia, and bipolar disorder. However, studies on circulating miRNAs for the diagnosis of heroin use disorders are rarely reported. In this study, we investigated the differential expression of plasma miRNAs in 57 heroin-dependent patients. Based on literature research and microarray analysis, two candidate miRNAs, miR-320a and let-7b-5p, were selected and analyzed by quantitative real-time RT-PCR. The results showed miR-320a and let-7b were significantly upregulated in plasma of the heroin-dependent patients compared to that in healthy controls. The area under curves (AUCs) of receiver operating characteristic (ROC) curves of miR-320a and let-7b-5p were 0.748 and 0.758, respectively. The sensitivities of miR-320a and let-7b-5p were 71.9 and 70.2%, while the specificities of miR-320a and let-7b-5p were 76.1 and 78.3%, respectively. The combination of these two miRNAs predicted heron dependence with an AUC of 0.782 (95% CI 0.687–0.876), with 73.7% sensitivity and 82.6% specificity. Our findings suggest a potential use for circulating miRNAs as biomarkers for the diagnosis of heroin abuse.

MicroRNA profiling in serum: Potential signatures for breast cancer diagnosis

2020 ◽  
pp. 1-13
Author(s):  
Xuan Zou ◽  
Tiansong Xia ◽  
Minghui Li ◽  
Tongshan Wang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mirna Expression ◽  
Expression Patterns ◽  
External Validation ◽  
Breast Cancer Diagnosis ◽  
Serum Samples ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Serum Exosomes

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC.

scholarly journals Comprehensive analysis on diagnostic value of circulating miRNAs for patients with ovarian cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (39) ◽  
pp. 66620-66628 ◽  
Author(s):  
Huiqing Wang ◽  
Tingting Wang ◽  
Wenpei Shi ◽  
Yuan Liu ◽  
Lizhang Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Diagnostic Value ◽  
Comprehensive Analysis ◽  
Circulating Mirnas

Circulating tumor DNA methylation as markers for early detection of pancreatic ductal adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 395-395
Author(s):  
Xiaoding Liu ◽  
Shiwei Guo ◽  
Chengcheng Ma ◽  
Yatong Li ◽  
Xiaoqian Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Detection ◽  
Circulating Tumor Dna ◽  
Detection Methods ◽  
Ductal Adenocarcinoma ◽  
Plasma Samples ◽  
Average Sensitivity ◽  
Reduced Representation ◽  
Non Invasive ◽  
Normal Plasma

395 Background: PDAC is a cancer of high mortality and low survival. Its early detection is critical due to symptoms often occur only at advanced stages. However there is no reliable screening tool to identify high-risk patients. ctDNA methylation has recently emerged as a promising new target to differentiate PDAC plasma from normal plasma for its early detection. Methods: Reduced representation bisulfite sequencing libraries were made in 46 PDAC tissues, 30 para-PDAC tissues and 20 PDAC plasmas to screen PDAC-specific markers, which was done by quantifying and comparing methylation levels of genomic regions and individual CpG sites between those groups. Markers were validated in plasma samples from 84 PDAC patients and 64 normal controls to propose a blood classifier. The best-performing markers were developed into a targeted sequencing panel, which was tested on a larger collection of plasma samples from patients of a variety of pancreatic diseases to build and validate a PDAC-predicting model. Results: We profiled genome-wide methylation patterns of tissues samples to identify 171 PDAC-specific markers. We reiterated training and cross-validating PDAC classification models using SVM method, and achieved an average sensitivity of 86% and specificity of 88%. To prove the feasibility of a non-invasive detection in plasma, a targeted methylation assay using those markers was tested on PDAC and normal plasmas, and yielded an average sensitivity of 68.4% and a specificity of 85.8%. We refined the panel by selecting the most discriminatory markers and built the version II of the panel, which was named PANcreatic Cancer Detection Assay, or PANDA, for a more efficient target capture, which was validated in an independent cohort of plasma samples that included 94 PDAC cases, 25 chronic pancreatitis (CP) cases and 80 normal samples from multiple centers. The PANDA achieved an AUC of 0.906 when classifying PDAC from normal, and an AUC of 0.882 when separating PDAC from CPs, both of which are more accurate than CA19-9, the conventional blood marker for PDAC. We further integrated test subjects’ age and their CA19-9 level as features into the PANDA model, which further elevated their AUC to 0.882 and 0.933 when classifying PDAC plasma from either CP plasma or normal plasma, respectively. Conclusions: We have developed PANDA, an NGS based target assay covering PDAC-specific DNA methylation targets by screening and validation on PDAC tissues and plasmas. Combined with age and CA19-9 blood level, PANDA has shown encouraging results to classify PDAC plasma from non-malignant diseases, demonstrating its potential to be optimized into non-invasive diagnostics for blood-based early PDAC screening.

Clinical competence of serum miR-372 expression in diagnosing prostate cancer

2020 ◽  
Author(s):  
Sheng Li ◽  
Xiaolan Ruan ◽  
Tongzu Liu
Keyword(s):  
Prostate Cancer ◽  
Expression Patterns ◽  
Specific Antigen ◽  
Diagnostic Value ◽  
Positive Lymph Node ◽  
Operating Characteristics ◽  
Serum Samples ◽  
Diagnostic Significance ◽  
Aberrant Expression ◽  
Poor Outcomes

Abstract Background: Prostate cancer (PCa) is considered as a serious healthy burden among males around the world. The limited diagnosis leads to poor outcomes of this malignancy. Aberrant expression of microRNAs (miRNAs) have been found in human cancers and play crucial roles in these malignant diseases. MicroRNA-372 (miR-372), as a type of miRNAs, has ever been investigated in various cancers. The purpose of the present study was to assess the expression patterns and diagnostic value of miR-372 in patients with PCa.Methods: 134 PCa patients and 68 healthy individuals were included in this study. The serum expression of miR-372 was examined by quantitative real-time PCR (qRT-PCR). To verify the diagnostic significance of miR-372, receiver operating characteristics (ROC) analysis was conducted for PCa patients.Results: Downregulated miR-372 expression was detected in serum samples collected from PCa patients compared with the healthy controls (P<0.001). The decreased expression of miR-372 was influenced by the positive lymph node metastasis (P=0.016), high prostate-specific antigen (PSA) concentration (P=0.002) and advanced TNM stage (P=0.013). The ROC curve was obtained with an AUC value of 0.896. At the cutoff value of 2.855, the sensitivity and specificity were 82.8% and 87.3%, respectively, suggesting the high diagnostic accuracy of miR-372.Conclusion: In summary, serum downregulated expression of miR-372 could serve as an efficient diagnostic biomarker for patients with PCa.

scholarly journals Degradation of serum microRNAs during transient storage of serum samples at 4℃

2017 ◽  
Vol 55 (1) ◽  
pp. 178-180 ◽  
Author(s):  
Toshiko Aiso ◽  
Shu Takigami ◽  
Akiko Yamaki ◽  
Hiroaki Ohnishi
Keyword(s):  
Extracellular Vesicles ◽  
Room Temperature ◽  
The Other ◽  
Transient Storage ◽  
Plasma Samples ◽  
Serum Samples ◽  
Prolonged Incubation ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
Serum Micrornas

Background Numerous studies demonstrate the potential of circulating microRNAs as non-invasive biomarkers for several diseases. Circulating microRNAs are much more stable than mRNAs and remain largely intact even after prolonged incubation at room temperature. However, recent reports show that microRNAs in serum or plasma samples have diverse stabilities. The aim of this pilot study is to evaluate the stabilities of miR-92a, miR-122 and miR-145 in serum during transient storage at 4℃ before freezing. Methods Serum samples were stored for 24 h at 4℃, and then RNA was extracted from whole serum or extracellular vesicles in serum. Total Exosome Isolation Reagent (from serum) was used for the fractionation of extracellular vesicles. Reverse transcription and real-time PCR of microRNAs were performed using the TaqMan MicroRNA Assays for miR-92a, miR-122 and miR-145. Results MiR-122 and miR-145 were degraded rapidly in serum; the concentrations dropped to 35.9% ( P < 0.001) and 29.3% ( P < 0.0001), respectively. These microRNAs in extracellular vesicles exhibited similar instability; the concentrations were 52.2% ( P < 0.05) and 56.5% ( P < 0.01), respectively. On the other hand, no significant degradation of miR-92a was observed (whole serum: P = 0.052, extracellular vesicles: P = 0.196). Conclusions MiR-122 and miR-145 in serum are extremely unstable and could be degraded during transient storage of serum at 4℃ prior to freezing.

Plasma microRNAs characterising patients with immune thrombo cytopenic purpura

2017 ◽  
Vol 117 (07) ◽  
pp. 1420-1431 ◽  
Author(s):  
Bin Zuo ◽  
Juping Zhai ◽  
Lifang You ◽  
Yunxiao Zhao ◽  
Jianfeng Yang ◽  
...  
Keyword(s):  
Therapy Response ◽  
Diagnostic Value ◽  
Healthy Controls ◽  
Circulating Mirnas ◽  
Characteristic Analysis ◽  
Mirna Microarray ◽  
Response Sets ◽  
Differentially Expressed Mirnas ◽  
Diagnostic Values ◽  
Plasma Mirnas

SummaryAltered microRNA (miRNA) expression has been reported in patients with immune thrombocytopenic purpura (ITP). However, the detailed expression profiling of cell-free circulating miRNAs in ITP patients has not been fully investigated. In this study, we aimed to examine plasma miRNAs in ITP patients and evaluate their diagnostic values. Plasma samples from 74 ITP patients and 58 healthy controls were obtained and allocated into discovery, validation, and therapy-response sets. Initial screen with a miRNA microarray assay identified 23 miRNAs with different levels between ITP patients and healthy controls (>1.5-fold changes; p<0.01). Subsequent quantitative real-time PCR confirmed eight up-regulated miRNAs (miR-320c, miR-642b-3p, miR-1275, miR-3141, miR-4270, miR-4499, miR-4739 and miR-6126) and three down-regulated miRNAs (miR-144–3p, miR-1281 and miR-3162–3p) in ITP patients. The levels of these circulating miRNAs varied, depending on ITP subtypes, i.e. newly-diagnosed, persistent and chronic ITP, and between treatment responders and non-responders. In receiver operator characteristic analysis, 10 miRNAs had positive diagnostic values (p<0.05) when tested individually. The diagnostic value improved when the miRNAs were analysed as a panel or together with the analysis of anti-platelet autoantibodies. Plasma miR-3162–3p levels were also found to positively correlate with platelet counts in ITP patients (r=0.338, p=0.01). Our results indicate that plasma miRNA profiles are altered in ITP patients and that the differentially expressed miRNAs may be used as biomarkers to improve the diagnosis of ITP.

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