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).

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.

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.

scholarly journals Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Serum Samples ◽  
Tissue Samples ◽  
Non Invasive ◽  
Specific Symptoms ◽  
Generation Sequencing

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

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 Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gulfem D. Guler ◽  
Yuhong Ning ◽  
Chin-Jen Ku ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Cell Free Dna ◽  
Early Stage Disease ◽  
Non Invasive ◽  
Cancer Pathogenesis ◽  
Free Dna ◽  
Stage Disease ◽  
Circulating Cell Free Dna

Abstract Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.

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 Identification of Circulating MiR-25 as a Potential Biomarker for Pancreatic Cancer Diagnosis

2016 ◽  
Vol 39 (5) ◽  
pp. 1716-1722 ◽  
Author(s):  
Ting Deng ◽  
Yaozong Yuan ◽  
Chunni Zhang ◽  
Chenyu Zhang ◽  
Weiyan Yao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Diagnosis ◽  
Diagnostic Value ◽  
Serum Tumor Marker ◽  
Quantitative Real Time Pcr ◽  
Serum Samples ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Potential Use ◽  
Normal Controls

Background: The aim of this study was to identify novel microRNAs for potential use in the diagnosis of pancreatic cancer (PaC). Methods: A total of 1063 serum samples from 303 patients with PaC were collected, and the expression level of miR-25 was measured using quantitative real-time PCR (qRT-PCR). Results: We found that miR-25 had significant diagnostic value for the differential diagnosis of PaC in normal controls with an AUC (the area under the ROC curve) of 0.915 (95% CI: 0.893-0.937) that was significantly higher compared with an AUC of 0.725 for serum tumor marker carcinoembryonic antigen (CEA) and an AUC of 0.844 for CA19-9. Conclusions: These data suggest that serum miR-25 has strong potential as a novel biomarker for the early detection of PaC.

scholarly journals Prognostic Significance and Immune Infiltration of Microenvironment‐related Signatures in Pancreatic Cancer

2020 ◽  
Author(s):  
Qian Lu ◽  
Yu Zhang ◽  
Weihong Gu ◽  
Xinrong Ji ◽  
Zhong Chen
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Immune Cell ◽  
Differential Expression Analysis ◽  
Prognostic Significance ◽  
Ductal Adenocarcinoma ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Tumor Tissues ◽  
Cox Analysis

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal and most aggressive types of malignancies and accounts for the vast majority of Pancreatic Cancer (PC). Numerous studies have reported that the tumor microenvironment (TME) was significantly correlated with the oncogenesis, progress, and prognosis of various malignancies. Therefore, mining of TME-related genes is reasonably important to improve the overall survival (OS) of patients with PDAC. Methods: The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to identify differential expressed genes (DEGs). Functional and pathway enrichment analyses, protein–protein interaction (PPI) network construction and module analysis, overall survival analysis and tumor immune estimation resource (TIMER) database analysis were then performed on DEGs. Results: Data analysis indicated that higher immune scores were correlated with better overall survival (P = 0.033). Differential expression analysis obtained 90 intersection genes influencing both stromal and immune scores. Among these intersection genes, CA9, EBI3, SPOCK2, WDFY4, CD1D and CCL22 were significantly correlated with OS in PDAC patients. Moreover, multivariate Cox analysis revealed that CA9, SPOCK2 and CD1D were the most significant prognostic genes, and were closely correlated with immune infiltration in TCGA cohort. Further analysis indicated that CD1D were significantly related with immune cell biomarkers for PDAC patients. Conclusions: In summary, our findings provide a more comprehensive insight into TME and show a list of prognostic immune associated genes in PDAC. However, further studies on these genes need to be performed to gain additional understanding of the association between TME and prognosis in PDAC.

scholarly journals Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

2018 ◽  
Author(s):  
Francois Collin ◽  
Yuhong Ning ◽  
Tierney Phillips ◽  
Erin McCarthy ◽  
Aaron Scott ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Training Data ◽  
Ductal Adenocarcinoma ◽  
Data Sets ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Pancreatic Cancers ◽  
Free Dna ◽  
Circulating Cell Free Dna

AbstractPancreatic cancers are typically diagnosed at late stage where disease prognosis is poor as exemplified by a 5-year survival rate of 8.2%. Earlier diagnosis would be beneficial by enabling surgical resection or earlier application of therapeutic regimens. We investigated the detection of pancreatic ductal adenocarcinoma (PDAC) in a non-invasive manner by interrogating changes in 5-hydroxymethylation cytosine status (5hmC) of circulating cell free DNA in the plasma of a PDAC cohort (n=51) in comparison with a non-cancer cohort (n=41). We found that 5hmC sites are enriched in a disease and stage specific manner in exons, 3’UTRs and transcription termination sites. Our data show that 5hmC density is reduced in promoters and histone H3K4me3-associated sites with progressive disease suggesting increased transcriptional activity. 5hmC density is differentially represented in thousands of genes, and a stringently filtered set of the most significant genes points to biology related to pancreas (GATA4, GATA6, PROX1, ONECUT1) and/or cancer development (YAP1, TEAD1, PROX1, ONECUT1, ONECUT2, IGF1 and IGF2). Regularized regression models were built using 5hmC densities in statistically filtered genes or a comprehensive set of highly variable 5hmC counts in genes and performed with an AUC = 0.94-0.96 on training data. We were able to test the ability to classify PDAC and non-cancer samples with the Elastic net and Lasso models on two external pancreatic cancer 5hmC data sets and found validation performance to be AUC = 0.74-0.97. The findings suggest that 5hmC changes enable classification of PDAC patients with high fidelity and are worthy of further investigation on larger cohorts of patient samples.

scholarly journals Diagnostic Value of Plasma miR-181b, miR-196a, and miR-210 Combination in Pancreatic Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Gongpan Liu ◽  
Cunhua Shao ◽  
Anyun Li ◽  
Xiaobin Zhang ◽  
Xingjun Guo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Vascular Invasion ◽  
Operating Characteristic ◽  
Clinical Stage ◽  
Diagnostic Value ◽  
Carbohydrate Antigen ◽  
Plasma Samples ◽  
Healthy Individuals ◽  
Qrt Pcr ◽  
Node Metastasis

Purpose. This study was aimed at investigating the roles of plasma miR-181b, miR-196a, and miR-210 in the diagnosis of pancreatic cancer (PC). Methods. Plasma samples were isolated from 40 patients with PC and 40 healthy individuals, respectively. The expression of miR-181b, miR-196a, and miR-210 was detected by qRT-PCR. The level of carbohydrate antigen 199 (CA199) was measured by an electrochemiluminescence (ECL) assay. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of miR-181b, miR-196a, miR-210, CA199, and their combinations in PC. Results. The expression of plasma miR-181b, miR-196a, and miR-210 was significantly upregulated in PC patients. The plasma level of CA199 was also significantly increased in PC patients. The expression of miR-181b, miR-196a, and miR-210 was closely associated with lymph node metastasis, clinical stage, and vascular invasion but not correlated with age, gender, and tumor size. miR-181b, miR-196a, and miR-210 have lower AUC than CA199 in the diagnosis of PC. miR-181b+miR-210 and miR-196a+miR-210 also have lower AUC than CA199. It is worth noting that miR-181b+miR-196a+miR-210 has a higher AUC than CA199 in the diagnosis of PC. Conclusion. The combination of plasma miR-181b, miR-196a, and miR-210 had a good diagnostic value for PC.

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