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Published in: Tumor Biology 10/2015

01-10-2015 | Research Article

Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma

Authors: Lin Chen, Feihu Chu, Yali Cao, Jianguo Shao, Feng Wang

Published in: Tumor Biology | Issue 10/2015

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Abstract

Previous studies have identified a number of microRNAs (miRNAs) that were aberrantly expressed in hepatocellular carcinoma (HCC) tissues. Nevertheless, their diagnostic and prognostic value in serum has not been fully evaluated. Herein, the levels of five serum miRNAs, namely, miR-182, miR-331-3p, miR-197, miR-492, and miR-581, were detected in 103 HCC patients, 95 benign liver diseases, and 40 healthy controls using real-time PCR technique. The results showed that, compared with benign liver diseases and healthy controls, the levels of serum miR-182 and miR-331-3p were significantly increased in HCC patients, both P < 0.001. Area under the receiver–operating characteristic (ROC) curves for serum miR-182 and miR-331-3p were 0.911 (95 % CI, 0.863–0.947) and 0.890 (95 % CI, 0.838–0.930), the sensitivity were 78.6 and 79.61 %, and the specificity were 91.58 and 86.32 %, respectively. Moreover, the combination of serum miR-182, miR-331-3p, and alpha-fetoprotein (AFP) can markedly increase the differential diagnostic value of benign and malignant liver diseases, especially better than serum AFP alone, P < 0.05. Serum miR-182 was positively correlated with serum AFP (P = 0.001), tumor size (P = 0.013), and TNM classification of malignant tumors (TNM) stage (P = 0.003); however, only TNM stage was demonstrated a significant correlation with serum miR-331-3p (P = 0.006). In addition, Kaplan–Meier survival curve, together with univariate and multivariate Cox proportional hazard analyses, further disclosed that serum miR-182 and miR-331-3p were associated with postoperative survival of HCC patients, and both of them were regarded to be independent prognostic factors for patients with HCC. Taken together, our present study indicates that serum miR-182 and miR-331-3p, upregulated in HCC, can provide positive diagnostic and prognostic values for HCC.
Literature
2.
go back to reference Xu WJ, Guo BL, Han YG, Shi L, Ma WS. Diagnostic value of alpha- fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumour Biol. 2014;35(12):12069–74.CrossRefPubMed Xu WJ, Guo BL, Han YG, Shi L, Ma WS. Diagnostic value of alpha- fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumour Biol. 2014;35(12):12069–74.CrossRefPubMed
3.
go back to reference Debruyne EN, Delanghe JR. Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta. 2008;395(1–2):19–26.CrossRefPubMed Debruyne EN, Delanghe JR. Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta. 2008;395(1–2):19–26.CrossRefPubMed
4.
go back to reference Park H, Park JY. Clinical significance of AFP and PIVKA-II responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma. Biomed Res Int. 2013;2013:310427.PubMedPubMedCentral Park H, Park JY. Clinical significance of AFP and PIVKA-II responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma. Biomed Res Int. 2013;2013:310427.PubMedPubMedCentral
5.
go back to reference Giannini EG, Sammito G, Farinati F, Ciccarese F, Pecorelli A, Rapaccini GL, et al. Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use. Cancer. 2014;120(14):2150–7.CrossRefPubMed Giannini EG, Sammito G, Farinati F, Ciccarese F, Pecorelli A, Rapaccini GL, et al. Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use. Cancer. 2014;120(14):2150–7.CrossRefPubMed
6.
go back to reference Han LL, Lv Y, Guo H, Ruan ZP, Nan KJ. Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy. World J Gastroenterol. 2014;20:10249–61.CrossRefPubMedPubMedCentral Han LL, Lv Y, Guo H, Ruan ZP, Nan KJ. Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy. World J Gastroenterol. 2014;20:10249–61.CrossRefPubMedPubMedCentral
8.
go back to reference Tutar L, Tutar E, Tutar Y. MicroRNAs and cancer; an overview. Curr Pharm Biotechnol. 2014;15:430–7.CrossRefPubMed Tutar L, Tutar E, Tutar Y. MicroRNAs and cancer; an overview. Curr Pharm Biotechnol. 2014;15:430–7.CrossRefPubMed
9.
go back to reference Berger F, Reiser MF. Micro-RNAs as potential new molecular biomarkers in oncology: have they reached relevance for the clinical imaging sciences? Theranostics. 2013;3:943–52.CrossRefPubMedPubMedCentral Berger F, Reiser MF. Micro-RNAs as potential new molecular biomarkers in oncology: have they reached relevance for the clinical imaging sciences? Theranostics. 2013;3:943–52.CrossRefPubMedPubMedCentral
10.
go back to reference Li B, Huang P, Qiu J, Liao Y, Hong J, Yuan Y. MicroRNA-130a is down- regulated in hepatocellular carcinoma and associates with poor prognosis. Med Oncol. 2014;31:230.CrossRefPubMed Li B, Huang P, Qiu J, Liao Y, Hong J, Yuan Y. MicroRNA-130a is down- regulated in hepatocellular carcinoma and associates with poor prognosis. Med Oncol. 2014;31:230.CrossRefPubMed
11.
go back to reference Chen P, Zhao X, Ma L. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;383:49–58.CrossRefPubMed Chen P, Zhao X, Ma L. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;383:49–58.CrossRefPubMed
12.
go back to reference Su ZX, Zhao J, Rong ZH, Geng WM, Wu YG, Qin CK. Upregulation of microRNA-25 associates with prognosis in hepatocellular carcinoma. Diagn Pathol. 2014;9:47.CrossRefPubMedPubMedCentral Su ZX, Zhao J, Rong ZH, Geng WM, Wu YG, Qin CK. Upregulation of microRNA-25 associates with prognosis in hepatocellular carcinoma. Diagn Pathol. 2014;9:47.CrossRefPubMedPubMedCentral
13.
go back to reference Gu H, Guo X, Zou L, Zhu H, Zhang J. Upregulation of microRNA-372 associates with tumor progression and prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;375:23–30.PubMed Gu H, Guo X, Zou L, Zhu H, Zhang J. Upregulation of microRNA-372 associates with tumor progression and prognosis in hepatocellular carcinoma. Mol Cell Biochem. 2013;375:23–30.PubMed
14.
go back to reference Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules. 2014;19:1912–38.CrossRefPubMed Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules. 2014;19:1912–38.CrossRefPubMed
15.
go back to reference Meng FL, Wang W, Jia WD. Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma. Med Oncol. 2014;31:177.CrossRefPubMed Meng FL, Wang W, Jia WD. Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma. Med Oncol. 2014;31:177.CrossRefPubMed
16.
go back to reference Zhang ZQ, Meng H, Wang N, Liang LN, Liu LN, Lu SM, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 2014;9:135.CrossRefPubMedPubMedCentral Zhang ZQ, Meng H, Wang N, Liang LN, Liu LN, Lu SM, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 2014;9:135.CrossRefPubMedPubMedCentral
17.
go back to reference Koberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, Peveling-Oberhag J, et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49:3442–9.CrossRefPubMed Koberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, Peveling-Oberhag J, et al. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 2013;49:3442–9.CrossRefPubMed
18.
go back to reference Zheng H, Liu JY, Song FJ, Chen KX. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer. Cancer Biol Med. 2013;10:123–30.PubMedPubMedCentral Zheng H, Liu JY, Song FJ, Chen KX. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer. Cancer Biol Med. 2013;10:123–30.PubMedPubMedCentral
19.
go back to reference Yang Y, Gu X, Zhou M, Xiang J, Chen Z. Serum microRNAs: a new diagnostic method for colorectal cancer. Biomed Rep. 2013;1:495–8.PubMedPubMedCentral Yang Y, Gu X, Zhou M, Xiang J, Chen Z. Serum microRNAs: a new diagnostic method for colorectal cancer. Biomed Rep. 2013;1:495–8.PubMedPubMedCentral
20.
go back to reference Yang MH, Yu J, Jiang DM, Li WL, Wang S, Ding YQ. microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis. J Transl Med. 2014;12:109.CrossRefPubMedPubMedCentral Yang MH, Yu J, Jiang DM, Li WL, Wang S, Ding YQ. microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis. J Transl Med. 2014;12:109.CrossRefPubMedPubMedCentral
21.
go back to reference Lei R, Tang J, Zhuang X, Deng R, Li G, Yu J, et al. Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene. 2014;33:1287–96.CrossRefPubMed Lei R, Tang J, Zhuang X, Deng R, Li G, Yu J, et al. Suppression of MIM by microRNA-182 activates RhoA and promotes breast cancer metastasis. Oncogene. 2014;33:1287–96.CrossRefPubMed
22.
go back to reference Zhu H, Fang J, Zhang J, Zhao Z, Liu L, Wang J, et al. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma. Biochem Biophys Res Commun. 2014;450:857–62.CrossRefPubMed Zhu H, Fang J, Zhang J, Zhao Z, Liu L, Wang J, et al. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma. Biochem Biophys Res Commun. 2014;450:857–62.CrossRefPubMed
23.
go back to reference Wang J, Li J, Shen J, Wang C, Yang L, Zhang X. MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma. BMC Cancer. 2012;12:227.CrossRefPubMedPubMedCentral Wang J, Li J, Shen J, Wang C, Yang L, Zhang X. MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma. BMC Cancer. 2012;12:227.CrossRefPubMedPubMedCentral
24.
go back to reference Qin J, Luo M, Qian H, Chen W. Upregulated miR-182 increases drug resistance in cisplatin-treated HCC cell by regulating TP53INP1. Gene. 2014;538:342–7.CrossRefPubMed Qin J, Luo M, Qian H, Chen W. Upregulated miR-182 increases drug resistance in cisplatin-treated HCC cell by regulating TP53INP1. Gene. 2014;538:342–7.CrossRefPubMed
25.
go back to reference Epis MR, Giles KM, Kalinowski FC, Barker A, Cohen RJ, Leedman PJ. Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells. J Biol Chem. 2012;287:35251–9.CrossRefPubMedPubMedCentral Epis MR, Giles KM, Kalinowski FC, Barker A, Cohen RJ, Leedman PJ. Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells. J Biol Chem. 2012;287:35251–9.CrossRefPubMedPubMedCentral
26.
go back to reference Guo X, Guo L, Ji J, Zhang J, Zhang J, Chen X, et al. miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. Biochem Biophys Res Commun. 2010;398:1–6.CrossRefPubMed Guo X, Guo L, Ji J, Zhang J, Zhang J, Chen X, et al. miRNA-331-3p directly targets E2F1 and induces growth arrest in human gastric cancer. Biochem Biophys Res Commun. 2010;398:1–6.CrossRefPubMed
27.
go back to reference Epis MR, Giles KM, Candy PA, Webster RJ, Leedman PJ. miR-331-3p regulates expression of neuropilin-2 in glioblastoma. J Neurooncol. 2014;116:67–75.CrossRefPubMed Epis MR, Giles KM, Candy PA, Webster RJ, Leedman PJ. miR-331-3p regulates expression of neuropilin-2 in glioblastoma. J Neurooncol. 2014;116:67–75.CrossRefPubMed
28.
go back to reference Chang RM, Yang H, Fang F, Xu JF, Yang LY. MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase. Hepatology. 2014;60:1251–63.CrossRefPubMed Chang RM, Yang H, Fang F, Xu JF, Yang LY. MicroRNA-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase. Hepatology. 2014;60:1251–63.CrossRefPubMed
Metadata
Title
Serum miR-182 and miR-331-3p as diagnostic and prognostic markers in patients with hepatocellular carcinoma
Authors
Lin Chen
Feihu Chu
Yali Cao
Jianguo Shao
Feng Wang
Publication date
01-10-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 10/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3430-2

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