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Exosomal miR-1246 in serum as a potential biomarker for early diagnosis of gastric cancer.

Abstract：

BACKGROUND:Gastric cancer (GC) patients are usually diagnosed in advanced stages which results in high mortality. This study aimed to identify novel circulating miRNAs as biomarkers for the early detection of GC. METHODS:Candidate miRNA was identified after integrated analysis of two Gene Expression Omnibus (GEO) datasets and clinical serum samples. Exosomes extracted were verified using transmission electron microscopy (TEM) and western blot. The expressions of miRNAs were tested through qRT-PCR. Receiver operating characteristic curve (ROC) analysis was used to explore the diagnostic utility of miRNAs. RNA pull-down assay was used to find RNA binding proteins (RBPs) which transport candidate miRNA into exosomes. Bioinformatics analysis of candidate miRNA was conducted using DAVID and Cytoscape. RESULTS:After integrated analysis of two GEO datasets, six circulating miRNAs were found to be consistently upregulated in GC patients. Then, qRT-PCR demonstrated that serum miR-1246 was the one with the largest fold change. Studies in vitro revealed that elevated serum miR-1246 was tumor-derived by being packaged into exosomes with the help of ELAVL1. Thereafter, we discovered that exosomal miR-1246 expressions in serum could differentiate GC patients with TNM stage I from healthy controls (HCs) and patients with benign diseases (BDs) with area under the curve (AUC) of 0.843 and 0.811, respectively. Bioinformatics analysis revealed miR-1246, as a tumor suppressor in GC, could regulate several signaling pathways. CONCLUSION:Circulating exosomal miR-1246 was a potential biomarker for the early diagnosis of GC.

journal_name

Int J Clin Oncol

journal_title

International journal of clinical oncology

authors

Shi Y,Wang Z,Zhu X,Chen L,Ma Y,Wang J,Yang X,Liu Z

doi

10.1007/s10147-019-01532-9

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

89-99

issue

1

eissn

1341-9625

issn

1437-7772

pii

10.1007/s10147-019-01532-9

journal_volume

25

pub_type

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