Dataset Information

MicroRNA-375 in extracellular vesicles - novel marker for esophageal cancer diagnosis.

ABSTRACT:

Background

MicroRNAs have been confirmed to function as diagnostic biomarkers for esophageal cancer (EC). This study aimed to investigate the diagnostic potential of miR-375 in the plasma or extracellular vesicles (EVs) of esophageal cancers (ECs).

Methods

miRNAs with diagnostic potential were identified through public database searches and validated through clinical sample testing. The diagnostic value of miR-375 in plasma and EVs was evaluated via receiver operating characteristic analysis and area under the curve. In addition, expression and survival analyses of the top ten target genes of miR-375 were conducted using the cancer genome atlas database.

Results

MiR-375 was identified as a potential biomarker for ECs by searching the gene expression omnibus database. Results of clinical sample measurements showed that miR-375 in plasma or EVs was significantly different between ECs and controls ( P < .01), but did not differ by gender or age. receiver operating characteristic analysis demonstrated that miR-375 in EVs could function as a diagnostic marker for ECs, with a higher area under the curve (0.852) than that in plasma. The expression and survival analysis of the top ten target genes for miR-375 showed that only EIF4G3 was significantly associated with survival ( P < .05).

Conclusion

This research shows that miR-375, particularly in EVs, could serve as a biomarker for the diagnosis of ECs.

SUBMITTER: Chen J

PROVIDER: S-EPMC9901947 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-375 in extracellular vesicles - novel marker for esophageal cancer diagnosis.

Chen Jie J Cai Zhigang Z Hu Jing J Zhou Lixia L Zhang Peili P Xu Xiaoping X

Medicine 20230201 5

<h4>Background</h4>MicroRNAs have been confirmed to function as diagnostic biomarkers for esophageal cancer (EC). This study aimed to investigate the diagnostic potential of miR-375 in the plasma or extracellular vesicles (EVs) of esophageal cancers (ECs).<h4>Methods</h4>miRNAs with diagnostic potential were identified through public database searches and validated through clinical sample testing. The diagnostic value of miR-375 in plasma and EVs was evaluated via receiver operating characterist ...[more]

PMID: 36749234

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Project description:BackgroundEsophageal cancer (ECa) is one of the most deadly cancers, with increasing incidence worldwide and poor prognosis. While endoscopy is recommended for the detection of ECa in high-risk individuals, it is not suitable for large-scale screening due to its invasiveness and inconvenience.MethodsIn this study, a novel gene methylation panel was developed for a blood-based test, and its diagnostic efficacy was evaluated using a cohort of 304 participants (203 cases, 101 controls). The assessment focused on the DNA methylation levels of SEPTIN9, tissue factor pathway inhibitor 2 (TFPI2), and the fragile histidine triad gene (FHIT) in patients with ECa, benign esophageal disease, and healthy controls. The receiver operating characteristic (ROC) curve was generated for the panel to calculate the area under the curve (AUC), sensitivity, specificity, and 95% confidence intervals (CIs), along with a comparison to the gold standard of pathological examination. The consistency between biomarker and pathological diagnosis was evaluated with kappa analysis conducted with IBM SPSS Statistics. The Chi-square test or Fisher's exact test was utilized to assess the association of test positivity with demographic characteristics.ResultsIn patients with ECa, SEPTIN9, TFPI2, and FHIT DNA methylation levels were significantly higher compared to those with benign esophageal disease or healthy controls. The panel demonstrated promising potential as a noninvasive tool for distinguishing malignant tumors from both healthy controls and benign esophageal diseases, achieving an area under the ROC curve of 0.925 (95% CI: 0.889-0.952), with a sensitivity of 79.8% [95% CI 73.6-85.1%] and specificity of 95.0% [95% CI 88.8-98.4%]. In particular, the panel showed exceptional diagnostic efficiency for stage 0, I, and II cancer patients with sensitivity at 69.0, 75.5%, and 78.9%, respectively. The comparison revealed a Kappa value of 0.725 between RT-PCR testing and the established gold standard of pathological examination, indicating a high level of consistency. Additionally, there was no bias in diagnostic efficiency based on age, gender, or the presence of other malignancies (non-esophageal cancers).ConclusionsThe study's findings suggested that the DNA methylation biomarkers panel holds promise as a non-invasive and convenient diagnostic test for ECa. The panel's ability to distinguish malignant tumors from benign esophageal diseases, coupled with its high sensitivity and specificity, presented opportunities to enhance the over-all diagnosis of high-risk population when in conjunction with existing detection methods.

Project description:Anaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers. Acute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP. A total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p<.0001). Precisely, the decrease of miR-375-3p correlated with the increase of two inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1) and granulocyte macrophage colony-stimulating factor (GM-CSF). On the other hand, functional and molecular data obtained showed that miR-375-3p partially blocked the endothelial barrier maintenance and stabilization by disassembly of cell-cell junctions exhibiting low Rac1-Cdc42 levels. These findings demonstrate a differential serum profile of circulating miRNAs in patients with anaphylaxis and exhibit the miR-375-3p modulation in serum and EVs during drug- and food-mediated anaphylactic reactions. Furthermore, the in silico and in vitro studies show a negative role for miR-375-3p/Rac1-Cdc42 in the endothelial barrier stability.

Dataset Information

MicroRNA-375 in extracellular vesicles - novel marker for esophageal cancer diagnosis.

Background

Methods

Results

Conclusion

Publications

MicroRNA-375 in extracellular vesicles - novel marker for esophageal cancer diagnosis.

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