Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma

Sohn, Woon Mok; Kim, Jong-Hwa; Kang, So Hee; Yang, Se Ra; Cho, Ju Yeon; Cho, Hyun Chin; Shim, Sang Goon; Paik, Yong Han

doi:10.1038/emm.2015.68

Cited by 361 publications

(264 citation statements)

References 48 publications

Supporting

Mentioning

249

Contrasting

Unclassified

Order By: Relevance

“…It was reported that miR-21 and miR-1246 were enriched in human breast cancer [66]. Sohn W's studies revealed that the levels of circulating exosomal miR-181, miR-221, and miR-224 were significant higher in HCC patients than in chronic hepatitis B patients; however, there were little differences in the level of circulating miRNAs between these two groups [67]. 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].…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…Previous studies have suggested that miR-224 may be a prospective biomarker for the diagnosis of HCC [41-43]. Okajima et al [44] performed a systematic review of microRNAs in plasma and identified miR-224 as a sensitive biomarker for detecting and monitoring HCC.…”

Section: Discussionmentioning

confidence: 99%

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

Zhang

Huang

Chen

2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

show abstract

“…The level and type of miRNA in the exosomes found in the serum of HCC patients differ significantly the miRNA in the serum exosomes of normal healthy individuals (67)(68)(69)(70). For instance, HCC patients with larger tumors and those with recurrent HCC after liver transplantation had lower levels of miR-718 in serumderived exosomes.…”

Section: Exosomes As Biological Markersmentioning

confidence: 93%

Exosome: An Emerging Participant in the Development of Liver Disease

Guo

Wang

et al. 2017

Hepat Mon

View full text Add to dashboard Cite

Context: An exosome is a type of extracellular vesicle with a diameter of 30 -100 nm and a density of 1.13 -1.19 g/m. Exosomes exist in almost all body fluids and can be secreted and absorbed by most cells. They deliver information and molecules that participate in intracellular communication, thus contributing to the progression of various diseases, such as liver diseases. Evidence Acquisition: In this study we collected and summarized the most important and new data available on the role of exosome in liver diseases by the PubMed search. The study data were collected through searching the related keywords then classified and summarized. Results: In this review, we summarize the research findings regarding the roles of exosomes in liver physiology and pathology, mainly focusing on liver diseases such as viral hepatitis, liver cancer (mostly hepatocellular carcinoma [HCC]), and liver injury caused by other pathogenic factors (alcohol, drugs, hepatotoxins, high-fat diets, parasites, etc.). Conclusions: These studies revealed the involvement of exosomes in various aspects of liver physiology and pathology and in the progress of liver diseases. More importantly, it offers a promising new direction for disease diagnosis and treatment.

show abstract

Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma

Cited by 361 publications

References 48 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

Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

Exosome: An Emerging Participant in the Development of Liver Disease

Contact Info

Product

Resources

About