Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma

被引:164
作者
Koeberle, Verena [1 ]
Kronenberger, Bernd [1 ]
Pleli, Thomas [1 ]
Trojan, Joerg [1 ]
Imelmann, Esther [1 ]
Peveling-Oberhag, Jan [1 ]
Welker, Martin-Walter [1 ]
Elhendawy, Mohammed [1 ]
Zeuzem, Stefan [1 ]
Piiper, Albrecht [1 ]
Waidmann, Oliver [1 ]
机构
[1] Johann Wolfgang Goethe Univ Hosp Frankfurt, Div Gastroenterol & Hepatol, Dept Med 1, D-60590 Frankfurt, Germany
关键词
HCC; microRNA; miR-1; miR-122; Prognostic marker; CIRCULATING MICRORNAS; PREDICT SURVIVAL; LIVER-CANCER; EXPRESSION; MIR-122; BIOMARKERS; SIGNATURES;
D O I
10.1016/j.ejca.2013.06.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The identification of new biomarkers to predict the aggressiveness of hepatocellular carcinoma (HCC) and supplement the current set of prognosis and treatment algorithms is an important clinical need. Extracellular microRNAs (miRNAs) circulating in the blood are a new class of highly promising disease markers. Aim: Here we investigated the prognostic potential of miR-1 and miR-122 in sera from patients with HCC. Methods: RNA was extracted from 195 sera of HCC patients and 54 patients with liver cirrhosis, obtained at the time of study enrolment. miR-1 and miR-122 levels were correlated with overall survival (OS), Cancer of the Liver Italian Program (CLIP) score, Barcelona Clinic Liver Cancer stage, clinical chemistry parameters and tumor specific treatment. Results: Patients with higher miR-1 and miR-122 serum levels showed longer OS than individuals with lower miR-1 and miR-122 serum concentrations (hazard ratio [HR] 0.440, 95% confidence interval [CI] 0.233-0.831, P = 0.011 for miR-1 and HR 0.493, 95% CI 0.254-0.956, P = 0.036 for miR-122, respectively). Serum miR-1 and miR-122 concentrations did not differ significantly between patients with HCC and liver cirrhosis. An age-, sex-, tumor stage and treatment-adjusted multivariate Cox regression analysis revealed that miR-1 serum levels (HR 0.451, 95% CI 0.228-0.856, P = 0.015) were independently associated with OS, whereas serum miR-122 was not. miR-1 serum levels showed no relevant correlation with clinical chemistry liver parameters, whereas serum miR-122 correlated with clinical chemistry parameters of hepatic necroinflammation, liver function and synthetic capacity. Conclusion: Our data indicate that serum miR-1 is a new independent parameter of OS in HCC patients and may therefore improve the predictive value of classical HCC staging scores. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3442 / 3449
页数:8
相关论文
共 47 条
  • [21] Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance
    Li, Jipeng
    Wang, Yiping
    Yu, Wanjun
    Chen, Jun
    Luo, Jianping
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 406 (01) : 70 - 73
  • [22] Serum microRNA Profiles Serve as Novel Biomarkers for HBV Infection and Diagnosis of HBV-Positive Hepatocarcinoma
    Li, Li-Min
    Hu, Zhi-Bin
    Zhou, Zhen-Xian
    Chen, Xi
    Liu, Fen-Yong
    Zhang, Jun-Feng
    Shen, Hong-Bing
    Zhang, Chen-Yu
    Zen, Ke
    [J]. CANCER RESEARCH, 2010, 70 (23) : 9798 - 9807
  • [23] Prognosis of hepatocellular carcinoma:: The BCLC staging classification
    Llovet, JM
    Brú, C
    Bruix, J
    [J]. SEMINARS IN LIVER DISEASE, 1999, 19 (03) : 329 - 338
  • [24] Hepatocellular carcinoma
    Llovet, JM
    Burroughs, A
    Bruix, J
    [J]. LANCET, 2003, 362 (9399) : 1907 - 1917
  • [25] Design and endpoints of clinical trials in hepatocellular carcinoma
    Llovet, Josep M.
    Di Bisceglie, Adrian M.
    Bruix, Jordi
    Kramer, Barnett S.
    Lencioni, Riccardo
    Zhu, Andrew X.
    Sherman, Morris
    Schwartz, Myron
    Lotze, Michael
    Talwalkar, Jayant
    Gores, Gregory J.
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2008, 100 (10): : 698 - 711
  • [26] Manghisi G, 1998, HEPATOLOGY, V28, P751
  • [27] Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis
    Mazzaferro, V
    Regalia, E
    Doci, R
    Andreola, S
    Pulvirenti, A
    Bozzetti, F
    Montalto, F
    Ammatuna, M
    Morabito, A
    Gennari, L
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (11) : 693 - 699
  • [28] Circulating microRNAs as stable blood-based markers for cancer detection
    Mitchell, Patrick S.
    Parkin, Rachael K.
    Kroh, Evan M.
    Fritz, Brian R.
    Wyman, Stacia K.
    Pogosova-Agadjanyan, Era L.
    Peterson, Amelia
    Noteboom, Jennifer
    O'Briant, Kathy C.
    Allen, April
    Lin, Daniel W.
    Urban, Nicole
    Drescher, Charles W.
    Knudsen, Beatrice S.
    Stirewalt, Derek L.
    Gentleman, Robert
    Vessella, Robert L.
    Nelson, Peter S.
    Martin, Daniel B.
    Tewari, Muneesh
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (30) : 10513 - 10518
  • [29] Papaconstantinou I, 2011, MOL CARCINOG
  • [30] Back to basics: Staging and prognosis in HCC for medical oncologist
    Peck-Radosavljevic, Markus
    [J]. JOURNAL OF HEPATOLOGY, 2012, 56 (02) : 488 - 489