scholarly journals Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Zhang ◽  
Huihui Li ◽  
Ming Yuan ◽  
Dong Li ◽  
Chang Sun ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Pcr Analysis ◽  
Go Annotation ◽  
Qrt Pcr ◽  
Noninvasive Biomarker ◽  
Novel Biomarkers ◽  
Negative Controls ◽  
Exosomal Mirna

Background. A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis. Methods. Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs. Results. A total of 24 miRNAs showed differential levels of enrichment with P<0.05 and log2 fold change>1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively. Conclusion. Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

scholarly journals Circulating expression of Hsa_circRNA_102893 contributes to early gestational diabetes mellitus detection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hongling Yang ◽  
Weitao Ye ◽  
Ruihua Chen ◽  
Fangling Zeng ◽  
Yan Long ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Early Pregnancy ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Qrt Pcr ◽  
Noninvasive Biomarker ◽  
Novel Biomarkers

Abstract Due to a poor availability of reliable biomarkers, detecting gestational diabetes mellitus (GDM) in early pregnancy remains a challenge. Novel biomarkers like Circular RNAs (circRNAs) may be a promising diagnostic tool. The aim of this study was (a) to identify circRNAs deregulated in GDM and (b) evaluate the potential of circRNAs in detecting GDM. The circRNAs expression profiling in 6 paired women (with and without GDM) was measured by microarray. The levels of five most relevant circRNAs were validated in 12 paired participants by qRT-PCR. To verify the reproducibility of qRT-PCR, significantly differential expressed circRNA levels were confirmed in 18 paired participants. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The areas under ROC curves of hsa_circRNA_102893 were 0.806 (95% CI 0.594–0.937) and 0.741 (0.568–0.872) in training set and test set, respectively. Circulating circRNAs reflect the presence of GDM. Hsa_circRNA_102893 may be a potential novel and stable noninvasive biomarker for detecting GDM in early pregnancy.

scholarly journals Urinary MicroRNA Biomarkers for Detecting The Presence of Esophageal Cancer

2020 ◽  
Author(s):  
Yusuke Okuda ◽  
Takaya Shimura ◽  
Hiroyasu Iwasaki ◽  
Shigeki Fukusada ◽  
Ruriko Nishigaki ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Poor Prognosis ◽  
Cross Validation ◽  
Area Under The Curve ◽  
Pcr Analysis ◽  
Discovery Cohort ◽  
Qrt Pcr ◽  
Urinary Levels ◽  
Noninvasive Biomarker ◽  
Test Sets

Abstract Background: Esophageal cancer (EC) including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) generally exhibits poor prognosis; hence, a noninvasive biomarker enabling early detection is necessary. Methods: Age- and sex-matched 150 healthy controls (HCs) and 43 patients with ESCC were randomly divided into two groups: 9 patients in the discovery cohort for microarray analysis and 184 patients in the training/test cohort with cross-validation for qRT-PCR analysis. Using 152 urine samples (144 HCs and 8 EACs), we validated the urinary miRNA biomarkers for EAC diagnosis.Results: Among eight miRNAs selected in the discovery cohort, urinary levels of five miRNAs (miR-1273f, miR-619-5p, miR-150-3p, miR-4327, and miR-3135b) were significantly higher in the ESCC group than in the HC group, in the training/test cohort. Consistently, these five urinary miRNAs were significantly different between HC and ESCC in both training and test sets. Especially, urinary miR-1273f and miR-619-5p showed excellent values of area under the curve (AUC) ≥ 0.80 for diagnosing stage I ESCC. Similarly, the EAC group had significantly higher urinary levels of these five miRNAs than the HC group, with AUC values of approximately 0.80.Conclusion: The present study established novel urinary miRNA biomarkers that can early detect ESCC and EAC.

scholarly journals A 3-circular RNA signature as a noninvasive biomarker for diagnosis of colorectal cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dao-xiong Ye ◽  
Si-si Wang ◽  
Ying Huang ◽  
Pan Chi
Keyword(s):  
Colorectal Cancer ◽  
Roc Curves ◽  
Circular Rna ◽  
Diagnostic Value ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Qrt Pcr ◽  
Noninvasive Biomarker ◽  
Proliferation And Metastasis ◽  
Polymerase Chain

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.

scholarly journals Urinary microRNA biomarkers for detecting the presence of esophageal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Okuda ◽  
Takaya Shimura ◽  
Hiroyasu Iwasaki ◽  
Shigeki Fukusada ◽  
Ruriko Nishigaki ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Poor Prognosis ◽  
Cross Validation ◽  
Area Under The Curve ◽  
Pcr Analysis ◽  
Discovery Cohort ◽  
Qrt Pcr ◽  
Urinary Levels ◽  
Noninvasive Biomarker ◽  
Test Sets

AbstractEsophageal cancer (EC) including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) generally exhibits poor prognosis; hence, a noninvasive biomarker enabling early detection is necessary. Age- and sex-matched 150 healthy controls (HCs) and 43 patients with ESCC were randomly divided into two groups: 9 individuals in the discovery cohort for microarray analysis and 184 individuals in the training/test cohort with cross-validation for qRT-PCR analysis. Using 152 urine samples (144 HCs and 8 EACs), we validated the urinary miRNA biomarkers for EAC diagnosis. Among eight miRNAs selected in the discovery cohort, urinary levels of five miRNAs (miR-1273f, miR-619-5p, miR-150-3p, miR-4327, and miR-3135b) were significantly higher in the ESCC group than in the HC group, in the training/test cohort. Consistently, these five urinary miRNAs were significantly different between HC and ESCC in both training and test sets. Especially, urinary miR-1273f and miR-619-5p showed excellent values of area under the curve (AUC) ≥ 0.80 for diagnosing stage I ESCC. Similarly, the EAC group had significantly higher urinary levels of these five miRNAs than the HC group, with AUC values of approximately 0.80. The present study established novel urinary miRNA biomarkers that can early detect ESCC and EAC.

scholarly journals Urinary microRNA Biomarkers for Detecting the Presence of Esophageal Cancer

2020 ◽  
Author(s):  
Yusuke Okuda ◽  
Takaya Shimura ◽  
Hiroyasu Iwasaki ◽  
Shigeki Fukusada ◽  
Ruriko Nishigaki ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Poor Prognosis ◽  
Cross Validation ◽  
Area Under The Curve ◽  
Pcr Analysis ◽  
Discovery Cohort ◽  
Qrt Pcr ◽  
Urinary Levels ◽  
Noninvasive Biomarker ◽  
Test Sets

Abstract Background: Esophageal cancer (EC) including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) generally exhibits poor prognosis; hence, a noninvasive biomarker enabling early detection is necessary. Thus, this study aimed to establish novel urinary miRNA biomarkers for diagnosing EC.Methods: Out of 343 patients (299 healthy controls [HCs] and 44 ESCCs), 150 HCs and 43 patients with ESCC, which were both age- and sex-matched, were analyzed and randomly divided into two groups: 9 patients (6 HCs and 3 ESCCs) in the discovery cohort for microarray analysis and 184 patients (144 HCs and 40 ESCCs) in the training/test cohort with cross-validation for qRT-PCR analysis. Using 152 urine samples (144 HCs and 8 EACs), we validated the urinary miRNA biomarkers for EAC diagnosis.Results: Eight miRNAs were selected as biomarker candidates in the discovery cohort. In the training/test cohort, five of the eight miRNAs (miR-1273f, miR-619-5p, miR-150-3p, miR-4327, and miR-3135b) in the ESCC group had significantly higher urinary levels than those in the HC group. Consistently, these five urinary miRNAs were significantly different between HC and ESCC in both training and test sets. Especially, urinary miR-1273f and miR-619-5p showed excellent values of area under the curve (AUC) ≥ 0.80 for diagnosing stage I ESCC. Consistent with the ESCC group, the EAC group had significantly higher urinary levels of these five miRNAs than the HC group, and it also exhibited AUC values of approximately 0.80.Conclusion: The present study established novel urinary miRNA biomarkers that can early detect ESCC and EAC.

scholarly journals P0614URINARY EXOSOMAL MICRORNA-21 AS A MARKER OF SCRUB TYPHUS-ASSOCIATED ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
In O Sun ◽  
Kwang Young Lee ◽  
A Young Cho
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Scrub Typhus ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Cross Sectional Study ◽  
Total Leukocyte Count ◽  
Cross Sectional ◽  
Exosomal Mirna

Abstract Background and Aims Urinary microRNA (miRNA)-21 is reported to be a biomarker for detection of acute kidney injury (AKI). Analysis of urinary exsome may serve as a novel diagnostic approach in kidney disease. The aim of this study is to investigate the clinical significance of urinary exosomal miRNA-21 for AKI in patients with scrub typhus. Method In a cross-sectional study, we collected 138 urine samples at the time of admission from 145 patients with scrub typhus. For 25 patients with scrub typhus-associated AKI and 25 age, sex-matched scrub typhus patient without AKI, we measured miRNA-21 in urinary exosomal fraction and compared diagnostic value in predictiong AKI. Results Compared with patients in the non-AKI group, patients in the AKI group were more likely to have one or more comorbidity such as diabetes (50% vs. 5%, P&lt;0.01) and chronic kidney disease (8% vs. 0%, P&lt;0.01). Total leukocyte count were higher in patients with AKI than in those without AKI (10.40 × 103/ mL vs. 6.40 × 103/mL, P&lt;0.01). The levels of urinary miRNA-21 were higher in the AKI group than in the non-AKI group. Urinary exosomal miRNA-21 levels correlated directly with serum neutrophil gelatinase-associated lipocalin values and total leukocyte counts and inversely with estimated glomerular filtration rate. The receiver operator characteristics curve analysis for urinary exosomal miRNA-21 showed good discriminative power for the diagnosis of scrub typhus-associated AKI, with area under the curve value of 0.907. Conclusion Urinary exosomal miRNA-21 could be a surrogate markers for the diagnosis of scrub typhus–associated AKI.

scholarly journals Circular RNA Expression Profiling Identifies Prostate Cancer- Specific circRNAs in Prostate Cancer

2018 ◽  
Vol 50 (5) ◽  
pp. 1903-1915 ◽  
Author(s):  
Qianlin Xia ◽  
Tao Ding ◽  
Guihong Zhang ◽  
Zehuan Li ◽  
Ling Zeng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Polymerase Chain Reaction Analysis ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Pcr Analysis ◽  
High Morbidity ◽  
Qrt Pcr ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers ◽  
Rna Expression Profiling

Background/Aims: Prostate cancer (PCa) is one of the main cancers that damage males’ health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. Methods: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. Results: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. Conclusion: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer.

scholarly journals Circulating miRNAs as Biomarkers for Prostate Cancer Diagnosis in Subjects with Benign Prostatic Hyperplasia

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wei Jin ◽  
Xiang Fei ◽  
Xia Wang ◽  
Fangjie Chen ◽  
Yan Song
Keyword(s):  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Statistical Tests ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Prostatic Hyperplasia ◽  
Control Group ◽  
Circulating Mirnas ◽  
Noninvasive Biomarker ◽  
Novel Biomarkers

Body fluids often contain freely circulating nucleic acids, many of which can be exploited as noninvasive tools for the diagnosis of cancer as well as for clinical prognostication. Identifying microRNAs (miRNAs) in subjects’ blood with various malignancies means that they can serve as novel biomarkers for prostate cancer (PCa) diagnosis. This study analyzed serum-circulating miRNAs as a noninvasive biomarker in subjects with PCa and subjects with benign prostatic hyperplasia (BPH). In total, 31 PCa subjects and 31 BPH subjects were included, with the BPH group serving as the control group. RT-qPCR was used to quantify the levels of 10 miRNAs, which included miR-18a, miR-34a, miR-106b, miR-183, miR-200a, miR-301a, miR-141, miR-182, miR-200b, and miR-375 in serum. Statistical tests were used to assess the relationship between the levels of miRNAs and the clinicopathological data. A significant increase was observed in the relative expression ratios of miR-141, miR-182, miR-200b, and miR-375 (1.89-, 2.09-, 2.41-, and 2.27-folds, respectively) in the PCa group when compared to the BPH group. Based on the receiver operating characteristic (ROC) analysis, the largest area under the curve (AUC), 0.923, was associated with the miR-200b group, indicating effective diagnostic properties for this biomarker. A correlation was observed between total prostate-specific antigen (TPSA) and the relative levels of miR-141, miR-182, miR-200b, and miR-375. The Gleason score and the miR-200b expression level were also correlated. These results are consistent with previous studies regarding the possibility of differentiating between PCa subjects and healthy controls based on the detection of miRNA. The findings attest to a distinctive expression profile of miRNA that is detectable in the blood of PCa subjects, thereby confirming the role of miRNAs as diagnostic biomarkers for PCa.

scholarly journals Circulating exosomal lncRNAs in patients with chronic coronary syndromes

2021 ◽  
Author(s):  
Meili Zheng ◽  
Ruijuan Han ◽  
Wen Yuan ◽  
Hongjie Chi ◽  
Yeping Zhang ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Case Control Study ◽  
Diagnostic Value ◽  
Pcr Analysis ◽  
Roc Curve Analysis ◽  
Coronary Syndrome ◽  
Qrt Pcr ◽  
Coronary Syndromes ◽  
European Society Of Cardiology ◽  
Control Study

IntroductionThe concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear.Material and methodsA case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients.ResultsA total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028).ConclusionsExosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

scholarly journals Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1059
Author(s):  
Sarah Atef Fahim ◽  
Mahmoud Salah Abdullah ◽  
Nancy A. Espinoza-Sánchez ◽  
Hebatallah Hassan ◽  
Ayman M. Ibrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diagnostic Accuracy ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Differentially Expressed Mirnas ◽  
E Box ◽  
Aggressive Breast Cancer ◽  
Potential Biomarkers

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.

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