Abstract
The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.
Highlights
Lung cancer is the most common, aggressive malignancy, which is related to the highest number of deaths worldwide [1,2,3]
The non-small cell lung cancer (NSCLC) group is composed of Squamous Cell Carcinoma (SCC), Adenocarcinoma (ADC), and Large Cell Carcinoma (LCC) [1,2,3,4]
The quantitative PCRs (qPCR) results (RQ values) for miRNAs were obtained for all NSCLC patients and control samples
Summary
Lung cancer is the most common, aggressive malignancy, which is related to the highest number of deaths worldwide [1,2,3]. Non-Small-Cell Lung Cancer (NSCLC—85%) [3,4]. Experimental and clinical studies showed that qualitative composition of extracellular vesicles (EVs) may serve as reliable biomarkers and early diagnostic factors of cancer disease [6].The EVs are composed of: exosomes, microvesicles and apoptotic bodies [7]. As functional carriers for intercellular communication, they contain thousands of active particles, such as various types of lipids, proteins, mRNA and microRNAs (miRNAs) [8,9]. They exert good stability in most body fluids, enabling delivery to the target tissue [6]. EVs are mediators of the constant communication between tumor cells and surrounding stromal cells during tumor invasion
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