Abstract
Lung cancer is the first leading cause of cancer deaths worldwide. Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence shows that long noncoding RNA (lncRNA) are capable of modulating tumor initiation, proliferation and metastasis. In the present study, we aimed to evaluate whether circulating lncRNA could be used as biomarkers for diagnosis and prognosis of NSCLC. Expression profiles of 14 lncRNA selected from other studies were validated in 20 pairs of tissues by quantitative real‐time PCR, and the dysregulated lncRNA thus identified were further validated in serum samples from two independent cohorts along with three tumor makers (CEA, CYFRA21‐1, and SCCA). Receiver‐operating characteristic analysis was utilized to estimate the diagnostic efficiency of the candidate lncRNA and tumor markers. Importantly, we observed an association between lncRNA expression and overall survival (OS) rate of NSCLC. The expressions of SOX2 overlapping transcript (SOX2OT) and ANRIL were obviously upregulated in NSCLC tissues and serum samples compared with normal controls (P < 0.01). Based on the data from the training set, we next used a logistic regression model to construct an NSCLC diagnostic panel consisting of two lncRNA and three tumor markers. The area under the curve of this panel was 0.853 (95% confidence interval = 0.804–0.894, sensitivity = 77.1%, specificity = 79.2%), and this was distinctly superior to any biomarker alone (all at P < 0.05). Similar results were observed in the validation set. Intriguingly, Kaplan–Meier analysis demonstrated that low expressions of SOX2OT and ANRIL were both associated with higher OS rate (P = 0.008 and 0.017, respectively), and SOX2OT could be used as an independent prognostic factor (P = 0.036). Taken together, our study demonstrated that the newly developed diagnostic panel consisting of SOX2OT, ANRIL, CEA, CYFRA21‐1, and SCCA could be valuable in NSCLC diagnosis. LncRNA SOX2OT and ANRIL might be ideal biomarkers for NSCLC prognosis.
Highlights
As one of the most common fatal tumors, lung cancer is the leading cause of cancer-related dysthanasia around the world (Chen et al, 2016; Fu et al, 2016; Siegel et al, 2017)
Our data showed that 12 Long noncoding RNA (lncRNA) were significantly dysregulated in Non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues (Table S2)
We assessed the expressions of the 12 lncRNA in 92 serum samples (46 NSCLCs and 46 healthy controls) and identified two lncRNA [SOX2 overlapping transcript (SOX2OT) and ANRIL] that were overexpressed in tumor serum samples compared with healthy controls (Table S3, all at P < 0.01)
Summary
As one of the most common fatal tumors, lung cancer is the leading cause of cancer-related dysthanasia around the world (Chen et al, 2016; Fu et al, 2016; Siegel et al, 2017). Some serum tumor markers, such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA) and cytokeratin 19 fragment (CYFRA21-1), are being employed extensively to diagnose NSCLC due to the rapid detection methods available (Chen et al, 2015; Zhao et al, 2015b). These serum markers exhibit very low sensitivity and specificity (I and Cho, 2015). We evaluated the association between lncRNA and prognosis of NSCLC in order to validate the feasibility of detecting NSCLC using circulating lncRNA
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