Plasma miR-145, miR-20a, miR-21 and miR-223 as novel biomarkers for screening early-stage non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the world. Late diagnosis is one of the most significant reasons for the high mortality rate of lung cancer. The identification of microRNAs (miRNAs) has opened a new field for molecular diagnosis of cancer. The purpose of the present study was to investigate whether plasma miRNAs may be used as biomarkers for early-stage NSCLC. A total of 232 participants, including 149 NSCLC patients and 83 healthy controls, were recruited between July 2012 and May 2014. We measured the levels of 10 miRNAs (miR-30d, miR-383, miR-20a, miR-145, miR-221, miR-25, miR-223, miR-21, miR-126 and miR-210) in plasma samples of 40 individuals (20 patients and 20 matched healthy controls) at the point of identification of disease, and 129 NSCLC patients and 83 healthy controls at the validation stage using reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristics (ROC) curves were generated for each possible combination of the miRNAs. We observed that the expression of plasma miR-145, miR-20a, miR-21 and miR-223 was significantly increased in the early-stage NSCLC samples compared with controls. miRNAs have significant diagnostic value for early-stage NSCLC. Combined ROC analyses using these four miRNAs revealed an elevated area under the ROC curve (AUC) of 0.897, with a sensitivity and specificity of 81.8 and 90.1%, respectively. This AUC helped in distinguishing early-stage NSCLC. Furthermore, the levels of the four plasma miRNAs were significantly decreased following surgery (P<0.05). Altered expression of miR-145, miR-20a, miR-21 and miR-223 in plasma are of tumor origin, and the four miRNAs may represent potential novel non-invasive biomarkers for early-stage NSCLC.

Effect of miR-21 on Apoptosis in Lung Cancer Cell Through Inhibiting the PI3K/ Akt/NF-κB Signaling Pathway in Vitro and in Vivo

“…Increasing evidence demonstrates that miRNAs were associated with the initiation and development process of non-small cell lung cancer (NSCLC) [25-27]. Recent studies demonstrated that miR-21 was up-regulated in non-small cell lung cancer [28]. In the present study, we showed that miR-21 was up-regulated in NSCLC cells compared with normal HBE cells.…”

A Strong Decrease in TIMP3 Expression Mediated by the Presence of miR-17 and 20a Enables Extracellular Matrix Remodeling in the NSCLC Lesion Surroundings

“…The present study assesses their expression in exosomes from peripheral blood samples of NSCLC patients, collected before and after surgical removal of the tumor, and compares our findings with data retrieved from TCGA. This approach to miR analysis is described in a few publications (51,52). In the present study, the miR-20a expression levels in pre-and postsurgical samples correlated positively.…”

Low serum miR‐223 expression predicts poor outcome in patients with acute myeloid leukemia

“…miR‐223 overexpression increased c‐Myc, cyclinD1, MMP7 protein levels which are related to cell proliferation and invasion, suggesting miR‐223 played an oncogenic role in colon cancer . In non‐small cell lung cancer (NSCLC), high miR‐223 expression was observed in sputum or blood samples of NSCLC patients, and ROC curve analysis revealed serum miR‐223 had high predictive accuracy in early‐stage NSCLC detection . The role of miR‐223 in human tumorigenesis seemed to be a double‐edged sword and its function might depend on tumor progression.…”

“…29 In non-small cell lung cancer (NSCLC), high miR-223 expression was observed in sputum or blood samples of NSCLC patients, and ROC curve analysis revealed serum miR-223 had high predictive accuracy in early-stage NSCLC detection. 30,31 The role of miR-223 in human tumorigenesis seemed to be a doubleedged sword and its function might depend on tumor progression. that in monocytes and significantly less than that found in granulocytes.…”