Abstract

BackgroundIn order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC.MethodsIn training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs.ResultsROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups.ConclusionsIn conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.

Highlights

  • Lung cancer causes extremely high mortality of cancer death worldwide, almost 85% of which are from non-small cell lung cancer (NSCLC) [1,2]

  • Pathological diagnosis based on biopsies remains to be the standard methods for early-stage NSCLC detection, such as bronchoscopy, which have an advantage over the other methods since it can dynamically monitor the aberrant conditions of lung, the invasive nature of this technique poses a potential risk on human body [4,5]

  • Selection of plasma miRNAs According to a large number of relevant articles which have reported the diagnostic value of miRNAs for NSCLC [11,17,18,19,20,21], we chose 12 miRNAs as our research target, including miR-30d, miR-383, miR-20a, miR-145, miR-221, miR-25, miR-223, miR-21, miR-126, miR-155, miR-182, and miR-210

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Summary

Introduction

Lung cancer causes extremely high mortality of cancer death worldwide, almost 85% of which are from non-small cell lung cancer (NSCLC) [1,2]. Still 75% of NSCLC cases are diagnosed in Currently, pathological diagnosis based on biopsies remains to be the standard methods for early-stage NSCLC detection, such as bronchoscopy, which have an advantage over the other methods since it can dynamically monitor the aberrant conditions of lung, the invasive nature of this technique poses a potential risk on human body [4,5] Imaging techniques, such as chest X-ray and computed tomography (CT), are used to detect earlystage NSCLC [6,7,8,9], but the exposure to the radiation may do harm to health. In order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC

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