Plasma microRNAs as potential biomarkers for non-small-cell lung cancer

Jun Shen, Nevins W Todd, Howard Zhang, Lei Yu, Xing Lingxiao, Yuping Mei, Maria Guarnera, Jipei Liao, Amy Chou, Changwan Larry Lu, Zhengran Jiang, HongBin Fang, Ruth L Katz, Feng Jiang, Jun Shen, Nevins W Todd, Howard Zhang, Lei Yu, Xing Lingxiao, Yuping Mei, Maria Guarnera, Jipei Liao, Amy Chou, Changwan Larry Lu, Zhengran Jiang, HongBin Fang, Ruth L Katz, Feng Jiang

Abstract

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Developing minimally invasive techniques that can diagnose NSCLC, particularly at an early stage, may improve its outcome. Using microarray platforms, we previously identified 12 microRNAs (miRNAs) the aberrant expressions of which in primary lung tumors are associated with early-stage NSCLC. Here, we extend our previous research by investigating whether the miRNAs could be used as potential plasma biomarkers for NSCLC. We initially validated expressions of the miRNAs in paired lung tumor tissues and plasma specimens from 28 stage I NSCLC patients by real-time quantitative reverse transcription PCR, and then evaluated diagnostic value of the plasma miRNAs in a cohort of 58 NSCLC patients and 29 healthy individuals. The altered miRNA expressions were reproducibly confirmed in the tumor tissues. The miRNAs were stably present and reliably measurable in plasma. Of the 12 miRNAs, five displayed significant concordance of the expression levels in plasma and the corresponding tumor tissues (all r>0.850, all P<0.05). A logistic regression model with the best prediction was defined on the basis of the four genes (miRNA-21, -126, -210, and 486-5p), yielding 86.22% sensitivity and 96.55% specificity in distinguishing NSCLC patients from the healthy controls. Furthermore, the panel of miRNAs produced 73.33% sensitivity and 96.55% specificity in identifying stage I NSCLC patients. In addition, the genes have higher sensitivity (91.67%) in diagnosis of lung adenocarcinomas compared with squamous cell carcinomas (82.35%) (P<0.05). Altered expressions of the miRNAs in plasma would provide potential blood-based biomarkers for NSCLC.

Figures

Figure 1
Figure 1
Receiver–operator characteristic (ROC) curve analysis of expression levels of the four miRNAs in plasma of 58 patients diagnosed with NSCLC and 29 healthy individuals. The area under the ROC curve (AUC) for each miRNA conveys its accuracy in differentiating NSCLC patients from the healthy subjects in terms of sensitivity and specificity. The individual genes produce 0.662–0.878 AUC values (a–d), being significantly lower than 0.926 AUC by the four genes genes used in combination as a marker panel (e) (all P<0.05).

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Source: PubMed

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