Abstract 4165: Combination of cell-free miR-198, carcinoembryonic antigen, and CYFRA 21-1 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion.

Abstract

Abstract Circulating cell-free microRNAs (miRNAs) have been identified as potential noninvasive biomarkers in cancer. The aim of this study was to identify miRNAs that are differentially expressed between benign pleural effusion (BPE) and lung adenocarcinoma-associated malignant pleural effusion (LA-MPE). We have also analyzed the expression of carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1, which are the most commonly used tumor markers in pleural effusion. Cell-free miRNA expression was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (10 BPEs and 10 LA-MPEs). The PANArrayTM miRNA expression profiling kit (PANAGENE, INC. Daejeon, Korea) was used to identify candidate miRNAs in the discovery set. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results obtained for the discovery set and those obtained for a validation set comprising 42 BPEs and 45 LA-MPEs. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the identified miRNAs, CEA, and CYFRA 21-1. Microarray profiling showed that miR-198 was significantly downregulated in LA-MPE compared with BPE (P = 0.002). The miRNA microarray analysis results were confirmed by qRT-PCR (P < 0.001) using the validation set. miR-198 showed an AUC of 0.887, with a sensitivity of 71.1% and a specificity of 95.2%. The AUC for CEA was 0.898, with a sensitivity of 78.4% and a specificity of 97.5%. The AUC for CYFRA 21-1 was 0.836, with a sensitivity of 78.4% and a specificity of 82.5%. The diagnostic performance of miR-198 was comparable with that of CEA, but better than that of CYFRA 21-1. The AUC for all three markers combined was 0.926 (95% confidence interval, 0.843-0.973) with a sensitivity of 89.2% and a specificity of 85.0%. The present study shows that expression of miR-198 was significantly downregulated in LA-MPE compared with BPE, and combination of cell-free miR-198, CEA and CYFRA 21-1 can be used to differentiate LA-MPE from BPE with a high degree of accuracy. These results suggest that miR-198 in pleural effusions may be a potential diagnostic biomarker for discriminating between BPE and LA-MPE. Citation Format: Hye Sook Han, Jieun Yun, Ok-Jun Lee. Combination of cell-free miR-198, carcinoembryonic antigen, and CYFRA 21-1 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4165. doi:10.1158/1538-7445.AM2013-4165