Peripheral Blood miR-328 Expression as a Potential Biomarker for the Early Diagnosis of NSCLC

Paola Ulivi,Wainer Zoli,Giovanni Foschi,Rosella Silvestrini,Emanuela Scarpi,Marta Mengozzi,Dino Amadori

doi:10.3390/ijms140510332

Abstract

Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral blood, thus representing potential diagnostic biomarkers. We evaluated 100 individuals comprising 86 patients with predominantly early-stage non-small cell lung cancer (NSCLC) and 24 healthy donors. RNA was extracted from peripheral blood samples and the expression of a panel of miRNAs was analyzed by Real-Time PCR method. Expression levels of miR-328, miR-18a, miR-339 and miR-140 were significantly higher in NSCLC patients than in healthy donors (p < 0.05). In particular, miR-328 showed good diagnostic accuracy in discriminating between patients with early NSCLC and healthy donors (AUC ROC 0.82, 95% CI 0.72–0.92), with 70% sensitivity and 83% specificity at the best relative expression cut-off of 300. Moreover, miR-339 was a good discriminant between healthy donors and late-stage NSCLC patients (AUC ROC 0.79, 95% CI 0.68–0.91). In conclusion, miR-328 represents a potential diagnostic biomarker of NSCLC, especially for the identification of early-stage tumors. Its role in discriminating between benign and malignant nodules detected by spiral CT warrants further investigation.

Highlights

Lung cancer is the leading cause of cancer death worldwide and five-year survival is closely correlated with tumor stage at the time of diagnosis
The best housekeeping miRNAs to analyze in peripheral blood were selected by evaluating the threshold cycle (Ct) values of RNU6B, RNU38B, RNU58A, RNU43 and RNU49 in 20 non-small cell lung cancer (NSCLC)
Ct values were inserted into geNorm software which identified

Summary

Introduction

Lung cancer is the leading cause of cancer death worldwide and five-year survival is closely correlated with tumor stage at the time of diagnosis. Detection could represent a promising strategy to increase curability and reduce mortality. A 20% reduction in mortality has been reported with the use of low-dose spiral computed tomography (CT) in high-risk individuals [1]. The radiation doses delivered and high costs limit the widespread application of this technique as a screening procedure [2]. The high rate of false-positives means that a large proportion of individuals undergo unnecessary follow-up and other diagnostic tests, including biopsy, further increasing costs and health risks [1,2,3].

Methods

Results

Conclusion