Popis: |
Background: The majority of lung cancer patients are diagnosed at an advanced or metastatic stage and their 5-year survival rate is < 5%. However, when patients are diagnosed at an early stage, Stage I, they have ~70% 5-year survival rate. The aim of the study was to identify Stage I lung cancer miRNA biomarkers for early lung cancer detection. Methods: RNA was isolated from serum of 11 healthy subjects and 45 non-small cell lung cancer (NSCLC) patients comprised of 21 Stage I, 8 Stage II and 11 Stage III adenocarcinoma (AC) and 5 squamous cell carcinoma (SCC) patients, and from NSCLC (A549, H23, H1437, H460 and H1299) and kidney (ACHN) cell lines. Eight miRNA lung cancer biomarker candidates were selected based on previously published studies, were analyzed by qRT-PCR/Taqman® analyses. Results: MiR486 levels were up-regulated in Stages I, II and III AC. Whereas MiR-122 and miR-29c were not detected in serum samples in most healthy subjects, these respective miRNAs were expressed in 62% and 71% of Stage I and 88% and 100% of Stage II and 91 and 100% of Stage III lung AC patients. Ratios of miR-486/miR-16 and miR-29c/miR-16 were ~10-fold higher in A549 lung AC cell lysates and media compared with renal ACHN cell lysates and media and both miRNAs were higher in A549 cells when compared to other lung cancer cell lines. Conclusions: Upregulation of miR-486 and miR-29c in blood can be used as a biomarker for early AC lung cancer diagnosis. |