Abstract

Molecular analysis of sputum presents a noninvasive approach for diagnosis of lung cancer. We have shown that dysregulation of small nucleolar RNAs (snoRNAs) plays a vital role in lung tumorigenesis. We have also identified six snoRNAs whose changes are associated with lung cancer. Here we investigated if analysis of the snoRNAs in sputum could provide a potential tool for diagnosis of lung cancer. Using qRT-PCR, we determined expressions of the six snoRNAs in sputum of a training set of 59 lung cancer patients and 61 cancer-free smokers to develop a biomarker panel, which was validated in a testing set of 67 lung cancer patients and 69 cancer-free smokers for the diagnostic performance. The snoRNAs were robustly measurable in sputum. In the training set, a panel of two snoRNA biomarkers (snoRD66 and snoRD78) was developed, producing 74.58% sensitivity and 83.61% specificity for identifying lung cancer. The snoRNA biomarkers had a significantly higher sensitivity (74.58%) compared with sputum cytology (45.76%) (P < 0.05). The changes of the snoRNAs were not associated with stage and histology of lung cancer (All P >0.05). The performance of the biomarker panel was confirmed in the testing cohort. We report for the first time that sputum snoRNA biomarkers might be useful to improve diagnosis of lung cancer.

Highlights

  • Lung cancer is the number one cancer killer in the USA and worldwide [1]

  • We focused on the six small nucleolar RNAs (snoRNAs) by first determining if they could be reliably detected in sputum. quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to determine expression levels of the six snoRNAs in RNA isolated from sputum of ten cancer-free individuals, respectively

  • To the best of our knowledge, this might be the first study to demonstrate that snoRNAs, middle-size ncRNAs, remain intact and are readily detectable in sputum

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Summary

Introduction

Tobacco smoking is the major cause of lung cancer [1]. Only 5-15% and less than 2% of patients with stage III and IV NSCLC are alive after five years [1]. These statistics provide the primary rationale to improve NSCLC early detection. A NCI-National Lung Screening Trail (NLST) showed that the early detection of lung cancer by using low-dose computed tomography (LDCT) significantly reduced the mortality [2]. LDCT has limited ability to differentiate malignant from benign pulmonary nodules (PNs), presenting a major clinical challenge for lung cancer early detection [3]. There is an urgent need for developing approaches that can improve diagnosis of NSCLC [3]

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