An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker

Goto, Takuma; Fujiya, Mikihiro; Konishi, Hiroaki; Sasajima, Junpei; Fujibayashi, Shugo; Hayashi, Akira; Utsumi, Tatsuya; Sato, Hiroki; Iwama, Takuya; Ijiri, Masami; Sakatani, Aki; Tanaka, Kazuyuki; Nomura, Yoshiki; Ueno, Nobuhiro; Kashima, Shin; Moriichi, Kentaro; Mizukami, Yusuke; Kohgo, Yutaka; Okumura, Toshikatsu

doi:10.1186/s12885-018-4006-5

Cited by 197 publications

(151 citation statements)

References 29 publications

(33 reference statements)

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“…The level of circulating exosomal miR-10b and miR-30c was significantly elevated in 29 PDAC patients relative to chronic pancreatitis patients; however, the level of CA 19-9 was normal or slightly increased in 8 cases [68]. Goto T's study showed that circulating exosomal miR-191, miR-21, and miR451a levels were superior to circulating miRNA levels for differentiating PDAC patients from intraductal papillary mucinous neoplasm (IPMN) patients [69]. Above all, it appears that circulating exosomal miRNA has a potential advantage over circulating miRNAs in PDAC diagnosis, whereas more work is required to compare its diagnostic value to that of tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

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Section: Discussionmentioning

confidence: 99%

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Zhang

Pan

et al. 2018

Cell Physiol Biochem

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“…Using the PDAC tissues, we examined the relationship between miR‐451a levels and CAB39 mRNA levels and demonstrated a significant inverse correlation. It has been reported that overexpression of miR‐21 downregulates the PDCD4, PTEN and TPM1 genes, promoting cancer progression . Using the PDAC tissues, we examined the association between miR‐21 levels and PDCD4 mRNA levels and showed a significant inverse correlation between them.…”

Section: Discussionmentioning

confidence: 91%

Exosome‐encapsulated microRNA‐4525, microRNA‐451a and microRNA‐21 in portal vein blood is a high‐sensitive liquid biomarker for the selection of high‐risk pancreatic ductal adenocarcinoma patients

Kawamura

Iinuma

Wada

et al. 2019

J Hepato Biliary Pancreat

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Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis. This is due to late diagnosis and lack of reliable prognostic biomarkers. In this study, we focused on exosomal microRNA (miRNA) in portal vein blood (PVB) as a potential biomarker to identify patients at high‐risk for recurrence and poor postoperative outcome. Methods Exosomal miR‐4525, miR‐451a and miR‐21 expressions were assessed using PVB and peripheral blood (PB) collected from 55 PDAC patients during curative pancreatectomy. Correlation between the miRNA expressions and clinical outcomes, and target genes expressions was investigated. Results Exosomal miR‐4525, miR‐451a and miR‐21 levels were upregulated in PVB, which were higher than those in the PB. High expression of miR‐4525, miR‐451a and miR‐21 in PVB was associated with recurrence with a higher sensitivity, specificity, and accuracy than that in PB. Cox regression analysis showed miR‐4525, miR‐451a and miR‐21 levels in PVB were independent prognostic factors for overall survival and disease‐free survival. There was a negative correlation between the expressions of miR‐4525 and MEN1 mRNA, miR‐451a and CAB39 mRNA, and t miR‐21 and PDCD4 mRNA. Conclusions miR‐4525, miR‐451a and miR‐21 in PVB are potential biomarkers identifying patients at high‐risk for recurrence and poor survival in resected PDAC patients.

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“…Huang et al first reported the use of deep sequencing to discover and characterize profiles of serum‐derived exosomal RNAs . Next generation sequencing was applied to discover serum exosomal RNAs in order to detect biomarkers of diseases . However, some challenges must be considered with regard to serum exosome research, including the difficulty of library construction from low concentration miRNAs, and of serum exosome miRNAs data normalization.…”

Section: Discussionmentioning

confidence: 99%

Serum exosomal microRNA let‐7i‐3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm

et al. 2019

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Kawasaki disease (KD) is a systemic vasculitis syndrome that leads to coronary artery aneurysm (CAA). While echocardiography is the most important imaging modality for coronary artery assessment, a specific diagnostic biomarker complementary for CAA has not been reported. We aimed to analyze the profiles of exosomal miRNAs extracted from the serum of KD patients and controls to identify candidate biomarkers for CAA. Serum samples from 39 healthy children, 42 CAA patients, 38 coronary artery dilatation (CAD) patients and 45 virus‐infected patients including 24 EBV patients and 21 ADV patients were randomly selected. Next generation sequencing was used to analyze serum exosomal miRNA to detect differentially expressed miRNAs. Biomarker candidates were validated by qRT‐PCR. One hundred (and) ninety‐six differentially expressed miRNAs (DEMs) were detected in CAA patients and healthy children. There were 70 DEMs and 140 DEMs in CAA patients versus CAD patients, and in CAA patients versus virus‐infected patients, respectively. We selected the three most upregulated (let‐7i‐3p, miR‐17‐3p, and miR‐210‐5p) and the three most downregulated miRNAs (miR‐6743‐5p, miR‐1246, and miR‐6834‐5p) in the DEMs, which were expressed differentially in CAA patients versus healthy children, and in CAA patients versus virus‐infected patients, not in virus‐infected patients versus healthy children, as biomarker candidates. Excluded DEMs of CAD and virus‐infected patients, let‐7i‐3p was detected by sequence data analysis as a biomarker candidate for CAA patients, and then validated by qRT‐PCR in a larger set of clinical samples. As a biomarker candidate, let‐7i‐3p provides an additional means of diagnosing CAA patients. Additionally, miRNA biomarkers complement ultrasonic imaging, allowing for greater diagnostic precision. © 2019 IUBMB Life, 2019

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An elevated expression of serum exosomal microRNA-191, − 21, −451a of pancreatic neoplasm is considered to be efficient diagnostic marker

Cited by 197 publications

References 29 publications

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Exosome‐encapsulated microRNA‐4525, microRNA‐451a and microRNA‐21 in portal vein blood is a high‐sensitive liquid biomarker for the selection of high‐risk pancreatic ductal adenocarcinoma patients

Serum exosomal microRNA let‐7i‐3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm

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