Plasma MicroRNA Panel to Diagnose Hepatitis B Virus-Related Hepatocellular Carcinoma

被引:587
作者
Zhou, Jian [1 ,2 ]
Yu, Lei [1 ]
Gao, Xue [2 ]
Hu, Jie [1 ]
Wang, Jiping [6 ]
Dai, Zhi [1 ]
Wang, Jie-Fei [3 ]
Zhang, Zhiyong [3 ]
Lu, Shaohua [4 ]
Huang, Xiaowu [1 ]
Wang, Zheng [1 ]
Qiu, Shuangjian [1 ]
Wang, Xiaoying [1 ]
Yang, Guohuan [1 ]
Sun, Huichuan [1 ]
Tang, Zhaoyou [1 ]
Wu, Ying [5 ]
Zhu, Hongguang [2 ,5 ]
Fan, Jia [1 ,2 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200433, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China
[3] Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China
[4] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China
[5] Fudan Univ, Shanghai Med Coll, Shanghai 200433, Peoples R China
[6] Harvard Univ, Sch Med, Bringham & Womens Hosp, Boston, MA USA
关键词
OPERATING CHARACTERISTIC CURVES; CIRCULATING MICRORNAS; ALPHA-FETOPROTEIN; SUPPRESSOR GENE; EXPRESSION; CANCER; BIOMARKERS; MIR-122; SERUM; TUMORS;
D O I
10.1200/JCO.2011.38.2697
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) -related HCC. Patients and Methods Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively. Conclusion We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy. J Clin Oncol 29: 4781-4788. (C) 2011 by American Society of Clinical Oncology
引用
收藏
页码:4781 / 4788
页数:8
相关论文
共 33 条
[1]  
AKEYAMA T, 1972, NEW ENGL J MED, V287, P989
[2]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[3]  
Chang Jinhong, 2004, RNA Biol, V1, P106, DOI 10.4161/rna.1.2.1066
[4]   Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties [J].
Coulouarn, C. ;
Factor, V. M. ;
Andersen, J. B. ;
Durkin, M. E. ;
Thorgeirsson, S. S. .
ONCOGENE, 2009, 28 (40) :3526-3536
[5]   COMPARING THE AREAS UNDER 2 OR MORE CORRELATED RECEIVER OPERATING CHARACTERISTIC CURVES - A NONPARAMETRIC APPROACH [J].
DELONG, ER ;
DELONG, DM ;
CLARKEPEARSON, DI .
BIOMETRICS, 1988, 44 (03) :837-845
[6]  
DIBISCEGLIE AM, 1989, CANCER, V64, P2117, DOI 10.1002/1097-0142(19891115)64:10<2117::AID-CNCR2820641024>3.0.CO
[7]  
2-7
[8]   MicroRNA expression and function in cancer [J].
Garzon, Ramiro ;
Fabbri, Muller ;
Cimmino, Amelia ;
Calin, George A. ;
Croce, Carlo M. .
TRENDS IN MOLECULAR MEDICINE, 2006, 12 (12) :580-587
[9]   Cyclin g1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma [J].
Gramantieri, Laura ;
Ferracin, Manuela ;
Fornari, Francesca ;
Veronese, Airtgelo ;
Sabbioni, Silvia ;
Liu, Chang-Gong ;
Calin, George A. ;
Giovannini, Catia ;
Ferrazzi, Eros ;
Grazi, Gian Luca ;
Croce, Carlo M. ;
Bolondi, Luigi ;
Negrini, Massimo .
CANCER RESEARCH, 2007, 67 (13) :6092-6099
[10]   A METHOD OF COMPARING THE AREAS UNDER RECEIVER OPERATING CHARACTERISTIC CURVES DERIVED FROM THE SAME CASES [J].
HANLEY, JA ;
MCNEIL, BJ .
RADIOLOGY, 1983, 148 (03) :839-843