Abstract LB-359: Plasma microRNAs as novel biomarkers for lung cancer

Abstract

Objective: Lung cancer is the leading cause of cancer-related deaths in both men and women. Since there is no validated population-based screening procedure, most patients with lung cancer are diagnosed at advanced stages with an overall five-year survival rate of only 15%. Therefore, diagnosis of lung cancer at an early stage is important for improving the outcome of patients. MicroRNAs (miRNAs), a family of 19- to 25-nucleotide and noncoding small RNAs that primarily function as gene regulators at post-transcriptional level, are frequently dysregulated in cancer. Recent studies demonstrate that the miRNAs in blood are present in notably stabile form and are readily detectible by various sensitive methods. This new finding has raised a concept that circulating miRNAs could be novel non-invasive biomarkers for cancer detection. The objective of this study is to investigate the potential of circulating microRNAs for lung cancer detection. Methods: First, we searched the miRNA microarray data of lung cancer from published literature, and selected 15 of miRNAs (miR-17, 21, 24, 106a, 125b, 128, 155, 182, 183, 197, 199b, 203, 205, 210 and 221) that were most frequently up-regulated in lung cancer tissues. Total RNA including miRNAs were isolated with mirVana PARIS kit (Ambion, TX), then polyadenylated and reverse-transcribed with a poly(T) adapter into cDNAs for real-time PCR using the miRNA-specific forward primer and the sequence complementary to the poly(T) adapter as the reverse primer. The levels of miRNAs were determined in 28 plasma samples from lung cancer patients and 16 of controls. Results: We found that the levels of miR-155, miR-182 and miR-197 in plasma of lung cancer patients were significantly elevated compared with controls. MiR-155 yielded an AUC (the areas under the ROC curve) of 0.8739 (95% CI:0.7489 to 0.9989, P<0.001), miR-182 yielded an AUC of 0.8426 (95% CI:0.7239 to 0.9614, P<0.001) and miR-197 yielded an AUC of 0.8037 (95% CI:0.6705 to 0.9369, P<0.001) in discriminating lung cancer from controls. Conclusions: MiR-155, miR-182 and miR-197 are significantly elevated in patient plasma with lung cancer and can be a potential non-invasive molecular biomarker for lung cancer screening and clinical follow-up. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-359.

Antitumor effect of miR-197 targeting in p53 wild-type lung cancer

“…MiR-197 was found to be overexpressed in lung, prostate and pancreas cancer tissues compared with normal specimen, [17][18][19] while levels of circulating miR-197 in combination with other miRNAs were used to generate a signature of biomarkers for early detection of lung cancer. 20,21 Moreover, increased expression of miR-197 contributes to carcinogenesis and it is considered a reliable marker for diagnosis, patient stratification and prognosis assessment in follicular thyroid carcinomas, [22][23][24] while promoting EMT and metastasis in pancreatic adenocarcinoma. Supported by these in vitro results, we hypothesized that miR-197 targeting may exert a therapeutic activity by inhibiting tumor growth in vivo.…”

Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer (Review)

“…The combination of these 3 miRNAs yielded 81.33% sensitivity and 86.76% specificity in discriminating lung cancer patients from controls. The levels of miR-155 and miR-197 were higher in the plasma from lung cancer patients with metastasis than in those without metastasis and were significantly decreased in responsive patients during chemotherapy (124). Different findings are reported by Heegaard et al that found that the expression of miRNA-146b, miRNA-221, let-7a, miRNA-155, miRNA-17-5p, miRNA-27a and miRNA-106a were significantly reduced in the serum of NSCLC cases while miRNA-29c was significantly increased.…”

Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients

“…[40][41][42][43] However to date no systematic evaluation of miRNA profiles in matched tissue and plasma samples has been performed in EEC patients. The source of plasma miRNAs has not been determined so far.…”