A serum exosomal microRNA panel as a potential biomarker test for gastric cancer.

Biochemical and Biophysical Research Communications(2017)

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摘要
The findings from several studies have suggested that circulating miRNAs are imbalanced with the genesis of gastric cancer (GC). Both normal and cancer cells can generate and secrete exosomes, which are nanosized membrane vesicles that can transport microRNAs and proteins. Emerging evidence indicates that the exosomes secreted by cancer cells can be released into the circulatory system. In this study, we investigated whether circulating exosomal miRNAs can be used to discriminate individuals with GC from healthy controls (NCs). Based on the quantitative reverse transcription polymerase chain reaction (qRT-PCR), four miRNAs (miR-19b-3p, miR-17-5p, miR-30a-5p, and miR-106a-5p) related to GC pathogenesis were identified in serum-circulating exosomes from a cohort of 20 healthy controls and 20 individuals with GC in the initial screening phase. The distinguished miRNAs were further validated in the training (90 GC vs. 90 NCs) and blinded phases 20 GC vs. 20 NCs), and the area under receiver operating characteristic (ROC) curves of these miRNAs were analyzed. We found that miR-19b and miR-106a were markedly overexpressed in individuals with GC compared to NCs (P < 0.0001). Besides, the ROC analyses yielded the AUC values of 0.786 for miR-106a-5p, 0.769 for miR-19b-3p and combined ROC analysis revealed the highest AUC value of 0.814 in discriminating GC patients from NCs. Furthermore, based on the model developed from the data, a signature composed of the 2 miRNAs (miR-19b-3p and miR-106a-5p) correctly discriminated 19 out of 20 GC serum samples (95% sensitivity) and 18 out of 20 normal samples (90% specificity) in the blinded phase. Moreover, the validated miRNAs were related to GC lymphatic metastasis (P < 0.01) and expressed at higher levels in stages III and IV compared to I and II stages (P < 0.05). These results suggest that serum exosomal miR-19b-3p and miR-106a-5p are novel potential biomarkers for detecting GC.
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关键词
Gastric cancer,miR-19b,miR-106a,Serum exosomes,Biomarkers
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