Identification Of Four Plasma MicroRNAs As Potential Biomarkers In The Diagnosis Of Male Lung Squamous Cell Carcinoma Patients In China

Background: With increasing incidence and mortality,lung cancer has become one of the most fatal malignancies internationally.Lung squamous cell carcinoma(LSCC)accounts for 25% of the total lung cancer,and 90% of them are male patients.Dysregulated micro RNAs(mi RNAs)in the plasma of patients with lung squamous cell carcinoma might serve as biomarkers for LSCC diagnosis.Methods: The expression of mi RNA was performed using quantitative reverse transcription polymerase chain reaction(q RT-PCR)on the basis of Exiqon panels in the initial screening phase including 3 male LSCC pool samples and 1 normal control(NC)pool sample(per 10 samples were pooled as 1 pool sample).After the training(32 LSCC VS.31 NCs),the testing(55 LSCC VS.55 NCs)and the external validation(15 LSCC VS.15 NCs)stage via q RT-PCR.Expression levels of identified mi RNAs were assessed in tissue samples(23 pairs)and plasma exosomes(16 LSCC VS.16 NCs).Receiver operating characteristic(ROC)curves were constructed to evaluate the diagnostic accuracy.Results: a four-mi RNA signature(miR-181a-5p,mi R-21-5p,mi R-106a-5p and mi R-93-5p)was identified for LSCC detection.Areas under the receiver operating characteristic curve(AUC)of the 4-mi RNA panel for the training,the testing and the external validation phase were 0.795,0.827 and 0.914,respectively.Then,the three mi RNAs(mi R-21-5p,mi R-106a-5p and mi R-93-5p)were explored in LSCC tissue samples,and their expression was significantly up-regulated,while mi R-181a-5p was founf down-regulated.However,none of the four mi RNAs found significantly up-regulated in plasma exosomes expect mi R-93-5p with borderline significance.Conclusions: Our study established a 4-mi RNA peripheral plasma signature which contributed to diagnosing male LSCC patients in China to a certain degree.