Six Serum-based MiRNAs As Potential Diagnostic Biomarkers For Gastric Cancer

Background:Gastric cancer(GC)is still a severe public health problem worldwide.Because of the lack of early diagnosis and late presentation,a fair number of gastric cancer patients were diagnosed at advanced stages.Compared to traditional tumor markers,serum microRNAs(miRNAs)may serve as promising diagnostic biomarkers for patients with gastric cancer.The aim of our study was to investigate serum miRNAs expression profile for GC diagnosis.Methods:Using quantitative reverse transcription polymerase chain reaction(qRT-PCR)based Exiqon panel(miRCURY-Ready-to-Use-PCR-Human-panel-I +II-V1.M)to perform expression profiling of peripheral serum miRNAs from 3 GC pool samples and 1 normal control(NC)pool in the initial screening phase.Identified miRNAs were further validated in the training(49 GC VS.47 NCs)and testing stages(154 GC VS.120 NCs)using qRT-PCR.The expression levels of the miRNAs were also explored in tissues,arterial serum and exosomes.Results:Consequently,a total of 58 miRNAs were identified through the initial screening phase,and 51 upregulated miRNAs and 7 downregulated miRNAs showed at least a 1.5-fold altered expression.These miRNAs were assessed in the training stage followed by validation in the testing stage and six serum miRNAs(miR-10b-5p,miR-132-3p,miR-185-5p,miR-195-5p,miR-20a-3p and miR-296-5p)were significantly overexpressed in GC compared with NCs.The areas under the receiver operating characteristic(ROC)curve of the six-miRNA panel were 0.764 and 0.702 for the training and testing stages,respectively.Further assessment revealed that miR-10b-5p and miR-296-5p were significantly up-regulated in GC tissues(n = 188).Additionally,patients who did not receive adjuvant chemotherapy with high expression of miR-10b-5p or miR-296-5p in tissues tended to suffer worse overall survival(OS).Furthermore,the expression levels of miR-10b-5p,miR-195-5p,miR-20a-3p and miR-296-5p were significantly elevated in exosomes from GC serum samples(n = 30).Conclusions:We identified a six-miRNA panel in serum which could serve as a non-invasive biomarker in the detection of GC.Background:Esophageal cancer is one of the most common worldwide cancers,particularly in China.Esophageal squamous cell carcinoma(ESCC)is the predominant histological subtype of esophageal cancer.Despite the improvements in perioperative management,ESCC patients still has a high probability of postoperative recurrence and metastasis because of delayed diagnosis.Circulating microRNAs(miRNAs)have been widely studied in various cancers;thus,we aim to screen miRNAs which could provide a novel diagnosis strategy for ESCC.Methods:We performed miRNA expression profling in the initial screening phase using quantitative reverse transcription polymerase chain reaction(qRT-PCR)based Exiqon panels from 3 ESCC pools and 1 normal control(NC)pool samples.Using qRT-PCR,identifed serum miRNAs were further confrmed in training(32 ESCC vs.32 NCs)and testing stages(108 ESCC vs.96 NCs).The diagnostic value of the identified miRNAs was validated by an external cohort(60 ESCC vs.60 NCs).The expression levels of the miRNAs were also determined in tissues,arterial serum,and exosomes.Results:In the initial screen stage,33 upregulated miRNAs and 3 downregulated miRNAs showed at least a 1.5-fold altered expression in 3 ESCC pooled samples compared to 1 NC pooled sample,respectively.These miRNAs were assessed in the training phase followed by validation in the testing phase,and 5 serum miRNAs(miR-20b-5p,miR-28-3p,miR-192-5p,miR-223-3p and miR-296-5p)were significantly overexpressed in the serum of ESCC patients compared with NCs.The areas under the receiver operating characteristic curve(ROC)of the five-miRNA signature were 0.753,0.763 and 0.966 for the training,testing and the external validation stages,respectively.MiR-20b-5p,miR-28-3p and miR-192-5p were significantly up-regulated in ESCC tissues,while miR-296-5p was overexpressed in ESCC serum exosomes.However,none of the five miRNAs showed significantly different expression between the arterial and peripheral serum.Conclusion:We identified a five-miRNA signature in serum for the detection of ESCC.