Downregulation of cell-free miR-198 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion.
Circulating cell-free microRNAs (miRNAs) are potential cancer biomarkers. 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). The expression level of cell-free miRNA was investigated in 107 patients with pleural effusion. Microarrays were used to screen 160 miRNAs in a discovery set comprising 20 effusion samples (ten BPEs and ten LA-MPEs). 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 and other common tumor markers, such as carcinoembryonic antigen (CEA) and cytokeratin fragment (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. The AUCs for miR-198, CEA and CYFRA 21-1 in the validation set were 0.887, 0.898 and 0.836, respectively. 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 suggests that cell-free miR-198 from patients with pleural effusion might have diagnostic potential for differentiating LA-MPE from BPE.
Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, South Korea.
Hye-Suk
HS
Han
Jieun
J
Yun
Sung-nam
SN
Lim
Joung-Ho
JH
Han
Ki Hyeong
KH
Lee
Seung Taik
ST
Kim
Min-Ho
MH
Kang
Seung-Myoung
SM
Son
Yong-Moon
YM
Lee
Song-Yi
SY
Choi
Seok Joong
SJ
Yun
Wun-Jae
WJ
Kim
Ok-Jun
OJ
Lee
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000097:blood*; D003937:Diagnosis, Differential; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000235:genetics*; D012372:ROC Curve; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C535221:MIRN198 microRNA, human; D035683:MicroRNAs; C102012:antigen CYFRA21.1