Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion
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PurposeThe accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancerpatients is important because MPE has a poor prognosis and is classified as stage IVdisease. Molecular biomarkers for pleural effusion, such as circulating extracellularmicroRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer(miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE). Materials and MethodsReal-time reverse transcription quantitative polymerase chain reaction was used tomeasure the expression of the three miRNAs in samples from 87 patients with pleuraleffusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The areaunder the receiver operating characteristic curve (AUC) was then used to evaluate thediagnostic performance of each of the three miRNAs and compare it with that of thecommon tumor marker, carcinoembryonic antigen (CEA). ResultsThe expression of all three miRNAs was significantly lower in LA-MPE than in BPE(p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882,0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased thediagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. ConclusionThe present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic valuewhen differentiating between LA-MPE and BPE.
Abstract
PurposeThe accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancerpatients is important because MPE has a poor prognosis and is classified as stage IVdisease. Molecular biomarkers for pleural effusion, such as circulating extracellularmicroRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer(miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE). Materials and MethodsReal-time reverse transcription quantitative polymerase chain reaction was used tomeasure the expression of the three miRNAs in samples from 87 patients with pleuraleffusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The areaunder the receiver operating characteristic curve (AUC) was then used to evaluate thediagnostic performance of each of the three miRNAs and compare it with that of thecommon tumor marker, carcinoembryonic antigen (CEA). ResultsThe expression of all three miRNAs was significantly lower in LA-MPE than in BPE(p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882,0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased thediagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. ConclusionThe present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic valuewhen differentiating between LA-MPE and BPE.
참고문헌 (25)
- Memon A, "Malignant effusions : diagnostic evaluation and therapeutic strategy", Curr Probl Cancer, 5, pp.1~30 (1981)
- Johnston WW, "The malignant pleural effusion : a review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients", Cancer, 56, pp.905~909 (1985)
- Goldstraw P, "The IASLC Lung Cancer Staging Project : proposals for the revision of the TNM stage groupings in the forthcoming(seventh)edition of the TNM classification of malignant tumours", J Thorac Oncol, 2, pp.706~714 (2007)
- See KC, "Advances in the diagnosis of pleural disease in lung cancer", Ther Adv Respir Dis, 5, pp.409~418 (2011)
- Nance KV, "Diagnostic efficacy of pleural biopsy as compared with that of pleural fluid examination", Mod Pathol, 4, pp.320~324 (1991)
- Gu P, "Diagnostic utility of pleural fluid carcinoembryonic antigen and CYFRA 21-1 in patients with pleural effusion : a systematic review and meta-analysis", J Clin Lab Anal, 21, pp.398~405 (2007)
- Bartels CL, "MicroRNAs : novel biomarkers for human cancer", Clin Chem, 55, pp.623~631 (2009)
- Cho WC, "MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy", Int J Biochem Cell Biol, 42, pp.1273~1281 (2010)
- Zhou L, "Circulating microRNAs in cancer : diagnostic and prognostic significance", Expert Rev Anticancer Ther, 12, pp.283~288 (2012)
- Cortez MA, "MicroRNAs in body fluids : the mix of hormones and biomarkers", Nat Rev Clin Oncol, 8, pp.467~477 (2011)
- Zhang X, "MiR-134 functions as a regulator of cell proliferation, apoptoapoptosis, and migration involving lung septation", In Vitro Cell Dev Biol Anim, 48, pp.131~136 (2012)
- Li J, "miR-134 inhibits epithelial to mesenchymal transition by targeting FOXM1 in non-small cell lung cancer cells", FEBS Lett, 586, pp.3761~3765 (2012)
- Takahashi Y, "MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines", PLoS One, 4, pp.e6677~ (2009)
- Ling B, "Tumor suppressor miR-22 suppresses lung cancer cell progression through posttranscriptional regulation of ErbB3", J Cancer Res Clin Oncol, 138, pp.1355~1361 (2012)
- Han HS, "Downregulation of cell-free miR-198 as a diagnostic biomarker for lung adenocarcinoma-associated malignant pleural effusion", Int J Cancer, 133, pp.645~652 (2013)
- Rabinowits G, "Exosomal microRNA : a diagnostic marker for lung cancer", Clin Lung Cancer, 10, pp.42~46 (2009)
- Xie L, "Cell-free miR-24 and miR-30d, potential diagnostic biomarkers in malignant effusions", Clin Biochem, 44, pp.216~220 (2011)
- Wang T, "Cellfree microRNA expression profiles in malignant effusion associated with patient survival in non-small cell lung cancer", PLoS One, 7, pp.e43268~ (2012)
- Johnson CD, "The let-7 microRNA represses cell proliferation pathways in human cells", Cancer Res, 67, pp.7713~7722 (2007)
- Liu H, "Identifying mRNA targets of microRNA dysregulated in cancer : with application to clear cell renal cell carcinoma", BMC Syst Biol, 4, pp.51~ (2010)
- Akcakaya P, "miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer", Int J Oncol, 39, pp.311~318 (2011)
- Yamakuchi M, "MicroRNA-22 regulates hypoxia signaling in colon cancer cells", PLoS One, 6, pp.e20291~ (2011)
- Zhang J, "microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity", Br J Cancer, 103, pp.1215~1220 (2010)
- Xu D, "miR-22 represses cancer progression by inducing cellular senescence", J Cell Biol, 193, pp.409~424 (2011)
- pyrene-7, 8-diol-9, 10-epoxide, "Toxicol In Vitro", 2010, 1168~1175