Ovarian cancer is one of the most threatening diseases among women in the world. Current detection methods are expensive and lack accuracy. Thus, a fast, non-invasive biomarker for detecting ovarian cancer is urgently needed. Compelling evidences have been demonstrated that microRNAs, a large family of single-stranded and non-protein-coding RNA molecules, can serve as useful biomarkers in cancer detection. In this study, the relative expressions of microRNA-145 (miR-145) in the serum of patients with ovarian cancer and healthy controls were investigated in an independent study. Subsequently, the diagnosis and prognosis value of miR-145 as a biomarker for ovarian cancer were examined. Furthermore, we performed a meta-analysis to summarize all the results from published studies and this study. Relative expressions of miR-145 were investigated in three independent groups (malignant ovarian cancer, benign ovarian tumor, and healthy controls), comprising a total of 270 participants. Receiver operating characteristic (ROC) curves and overall survival (OS) curves were conducted to compare miR-145 level and clinical characteristics among the three groups. The results showed that relative expressions of the serum miR-145 were significantly down-regulated in patients with malignant ovarian cancer and benign ovarian cancer, compared to healthy controls (P < 0.01). Serum miR-145 levels could discriminate patients with malignant ovarian cancer from healthy controls, with a power area under the curve (AUC) of 0.82 (95 % confidence interval (CI) = 0.77–0.88). Furthermore, patients with low serum levels of miR-145 had a significantly shorter median overall survival rate (hazard ratio (HR) = 1.81, 95 % CI = 1.03–3.17, P = 0.039). The meta-analysis yields good diagnostic performances of miR-145 in various cancers, with an AUC of 0.82 (95 % CI, 0.78–0.85). In conclusion, the present study suggested that miR-145 can potentially serve as an outstanding biomarker for ovarian and other human cancers detection.
Ovarian cancer MicroRNA MicroRNA-145 Serum Biomarker Diagnosis Prognosis
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This work is supported by the “Mechanism of PTEN/P13K Signaling Pathway in Reconstruction of Ovary by In Situ Transplantation of Placental Mesenchymal Stem Cells” (Guangdong Health Bureau, A2013516) and “Mechanism of the Sensitizing Effect of CENP-H in Paclitaxel Chemotherapy for Breast Cancer” (National Natural Science Foundation, 81101682). The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Conflicts of interest
Bandera CA. Advances in the understanding of risk factors for ovarian cancer. J Reprod Med. 2005;50:399–406.PubMedGoogle Scholar
Ahmed FY, Wiltshaw E, A’Hern RP, Nicol B, Shepherd J, Blake P, et al. Natural history and prognosis of untreated stage I epithelial ovarian carcinoma. J Clin Oncol. 1996;14:2968–75.CrossRefPubMedGoogle Scholar
Zohny SF, Fayed ST. Clinical utility of circulating matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) as markers for diagnosis of epithelial ovarian cancer. Med Oncol. 2010;27:1246–53. doi:10.1007/s12032-009-9366-x.CrossRefPubMedGoogle Scholar
Havrilesky LJ, Whitehead CM, Rubatt JM, Cheek RL, Groelke J, He Q, et al. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 2008;110:374–82. doi:10.1016/j.ygyno.2008.04.041.CrossRefPubMedGoogle Scholar
Tolle A, Jung M, Rabenhorst S, Kilic E, Jung K, Weikert S. Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer. Oncol Rep. 2013;30:1949–56. doi:10.3892/or.2013.2621.PubMedGoogle Scholar
Zhang W, Wang Q, Yu M, Wu N, Wang H. MicroRNA-145 function as a cell growth repressor by directly targeting c-Myc in human ovarian cancer. Technol Cancer Res Treat. 2014;13:161–8. doi:10.7785/tcrt.2012.500367.PubMedGoogle Scholar
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006. doi:10.1038/cr.2008.282.CrossRefPubMedGoogle Scholar
Yang C, Wang C, Chen X, Chen S, Zhang Y, Zhi F, et al. Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas. Int J Cancer. 2013;132:116–27. doi:10.1002/ijc.27657.CrossRefPubMedGoogle Scholar
Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, et al. A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer. 2011;47:784–91. doi:10.1016/j.ejca.2010.10.025.CrossRefPubMedGoogle Scholar
Ichimi T, Enokida H, Okuno Y, Kunimoto R, Chiyomaru T, Kawamoto K, et al. Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int J Cancer. 2009;125:345–52. doi:10.1002/ijc.24390.CrossRefPubMedGoogle Scholar
Wach S, Nolte E, Szczyrba J, Stohr R, Hartmann A, Orntoft T, et al. MicroRNA profiles of prostate carcinoma detected by multiplatform microRNA screening. Int J Cancer. 2012;130:611–21. doi:10.1002/ijc.26064.CrossRefPubMedGoogle Scholar
Yun SJ, Jeong P, Kim WT, Kim TH, Lee YS, Song PH, et al. Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer. Int J Oncol. 2012;41:1871–8. doi:10.3892/ijo.2012.1622.PubMedGoogle Scholar
Mar-Aguilar F, Mendoza-Ramirez JA, Malagon-Santiago I, Espino-Silva PK, Santuario-Facio SK, Ruiz-Flores P, et al. Serum circulating microRNA profiling for identification of potential breast cancer biomarkers. Dis Markers. 2013;34:163–9. doi:10.3233/dma-120957.CrossRefPubMedPubMedCentralGoogle Scholar
Cuk K, Zucknick M, Heil J, Madhavan D, Schott S, Turchinovich A, et al. Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer. 2013;132:1602–12. doi:10.1002/ijc.27799.CrossRefPubMedGoogle Scholar
Doberstein K, Steinmeyer N, Hartmetz AK, Eberhardt W, Mittelbronn M, Harter PN, et al. MicroRNA-145 targets the metalloprotease ADAM17 and is suppressed in renal cell carcinoma patients. Neoplasia. 2013;15:218–30.CrossRefPubMedPubMedCentralGoogle Scholar