Study on circulating miR-17-5p/miR-362-5p as a blood biomarker for lung squamous cell carcinoma
Objective To screen differentially expressed microRNAs(miRNAs)in the blood of patients with lung squamous cell carcinoma(LUSC),which can be used as diagnostic biomarkers.Methods The differen-tially expressed mirnas in whole blood of 6 LUSC patients and 6 age-matched healthy controls were randomly selected by miRNA microarray,and then the candidate differentially expressed miRNAs were verified by real-time polymerase chain reaction in 35 LUSC patients and 33 healthy controls.Results Six differently ex-pressed miRNAs in serum samples(miR-17-5p,miR-205-5p,miR-362-5p,miR-21-5p,miR-210-3p,and miR-222-3p)were found in LUSC patients.Among them,miR-17-5p,miR-362-5p and miR-21-5p could well distinguish the LUSC group and the control group,and the area under the receiver operator characteristic curve(ROC AUC)were all>0.8(P<0.001),indicating relatively higher AUC,sensitivity and specificity than the other three miRNAs.Moreover,miR-17-5p and miR-362-5p could well distinguish the early stage(TNM stage Ⅰ-Ⅱ)LUSC patients from healthy control volunteers,with AUC values>0.8(P<0.001).Data from the TCGA database showed that high expression of miR-17-5p or miR-362-5p predicted poor overall survival in LUSC patients(n=332 cases)(log-rank P<0.05).Logistic regression analysis was performed with the occur-rence of LUSC as the dependent variable and the expression of miR-17-5p and miR-362-5p combination(2-miRNA panel)as the indepedent variable,to determine whether the 2-miRNA combination could improve the diagnostic value.The AUC of 2-miRNA panel was 0.9570,and the sensitivity and specificity were 92.65%and 92.31%,respectively.Bioinformatics analysis suggests that these two miRNAs may be involved in a variety of cancer-related pathways.Conclusion MiR-17-5p and miR-362-5p can accurately distinguish between LUSC patients and healthy control groups,and effectively predict the adverse survival rate of LUSC patients.It is considered that 2-miRNA panel can be used as candidate biomarkers for LUSC diagnosis,but further research is needed to demonstrate it.