Abstract
Various studies have demonstrated the diagnostic value of microRNA (miRNA) for lung cancer, but miRNA signatures varied between different subtypes. Whether serum miRNAs could be used as biomarkers in lung squamous cell carcinoma (SCC) remains unknown. Using quantitative real-time polymerase chain reaction (qRT-PCR) based Exiqon panel, 38 differentially expressed miRNAs were identified from 3 male lung SCC pool samples and 1 normal control (NC) pool in the initial screening phase. After the training (24 SCC VS. 15 NCs), testing (44 SCC VS. 57 NCs) and external validation (34 SCC VS. 36 NCs VS. 10 pulmonary hamartoma) processes via qRT-PCR, we identified a three-miRNA panel ((miR-106a-5p, miR-20a-5p and miR-93-5p) to be a potential diagnostic marker for male lung SCC patients. The areas under the receiver operating characteristic (ROC) curve of the three-miRNA panel for the training, testing and validation phases were 0.969, 0.881 and 0.954 respectively. In addition, this signature could also differentiate lung SCC from pulmonary hamartoma (AUC=0.900). The 3 miRNAs were consistently up-regulated in lung SCC tissues (23 SCC VS. 23 NCs) and serum exosomes (17 SCC VS. 24 NCs). Moreover, expression of the 3 miRNAs was decreased in arterial serum (n = 3). In conclusion, we established a three-miRNA signature in the peripheral serum with considerable clinical value in the diagnosis of male lung SCC patients.
Highlights
Lung cancer is the leading cause of cancer mortality in both men and women worldwide [1]
After the training (24 squamous cell carcinoma (SCC) VS. 15 normal control (NC)), testing (44 SCC VS. 57 NCs) and external validation (34 SCC VS. 36 NCs VS. 10 pulmonary hamartoma) processes via quantitative real-time polymerase chain reaction (qRTPCR), we identified a three-miRNA panel ((miR-106a-5p, miR-20a-5p and miR-935p) to be a potential diagnostic marker for male lung SCC patients
As a result of our multiphase analysis, we identified a three-miRNA panel to be the potential signature for the detection of male lung SCC patients (Figure 2)
Summary
Lung cancer is the leading cause of cancer mortality in both men and women worldwide [1]. Among NSCLCs, squamous cell carcinoma (SCC) is one of the major histological subtypes [2]. The majority of lung SCC patients is male and had a smoking history [3, 4]. Surgical resection shows promise in treating lung SCC, a lack of effective tools for early diagnose leads to low 5-year survival rates [2]. Low-dose computed tomography (LDCT) has been explored as a method for the diagnosis of early lung SCC, it still has several limitations [5]. None-invasive markers such as squamous cell carcinoma antigen (SCC Ag), neuron-specific enolase (NSE) and Cyfra 21-1 are not sensitive and specific enough for the routine use in the diagnose of lung SCC [6]. New and non-invasive biomarkers with high diagnostic power for lung SCC patients are urgently needed
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