Serum MicroRNAs as Biomarkers for Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection

被引:242
作者
Qi, Peng [1 ]
Cheng, Shu-qun [2 ]
Wang, Hao [3 ]
Li, Nan [2 ]
Chen, Yue-feng [1 ]
Gao, Chun-fang [1 ]
机构
[1] Second Mil Med Univ, Eastern Hepatobiliary Hosp, Dept Lab Med, Shanghai, Peoples R China
[2] Second Mil Med Univ, Eastern Hepatobiliary Hosp, Dept Oncol Comprehens Treatment, Shanghai, Peoples R China
[3] Second Mil Med Univ, Dept Lab Med, Changzheng Hosp, Shanghai, Peoples R China
来源
PLOS ONE | 2011年 / 6卷 / 12期
基金
中国国家自然科学基金;
关键词
NON-TUMOROUS TISSUES; CIRCULATING MICRORNAS; C VIRUS; EXPRESSION PATTERNS; PLASMA MICRORNAS; OVARIAN-CANCER; IN-VIVO; MIR-122; INJURY; CELLS;
D O I
10.1371/journal.pone.0028486
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for hepatocellular carcinoma (HCC). Methodology/Principal Findings: This study was divided into four phases: (I) Ten candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 10 HCC patients with chronic hepatitis B virus (HBV) infection and 10 age-and sex-matched healthy subjects. (II) Marker validation by real-time RT-PCR on HBV patients with (n = 48) or without HCC (n = 48), and healthy subjects (n = 24). (III) Marker detection by real-time RT-PCR in sera from another 14 HCC patients before and 1 month after surgical resection. (IV) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients. Although miR-222, miR-223 or miR-21 were significantly up-or down-regulated between HCC patients and healthy controls, no significant difference was observed in the levels of these miRNAs between HBV patients without and with HCC. MiR-122 in serum was significantly higher in HCC patients than healthy controls (p<0.001). More importantly, it was found that the levels of miR-122 were significantly reduced in the post-operative serum samples when compared to the pre-operative samples. Although serum miR-122 was also elevated in HBV patients with HCC comparing with those without HCC, the difference was at the border line (p = 0.043). Conclusions/Significance: Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of HCC in healthy subjects, moreover, it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients.
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页数:8
相关论文
共 45 条
[1]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[2]   Liver-specific MicroRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells [J].
Chang, Jinhong ;
Cruo, Ju-Tao ;
Jiang, Dong ;
Guo, Haitao ;
Taylor, John M. ;
Block, Timothy M. .
JOURNAL OF VIROLOGY, 2008, 82 (16) :8215-8223
[3]   Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases [J].
Chen, Xi ;
Ba, Yi ;
Ma, Lijia ;
Cai, Xing ;
Yin, Yuan ;
Wang, Kehui ;
Guo, Jigang ;
Zhang, Yujing ;
Chen, Jiangning ;
Guo, Xing ;
Li, Qibin ;
Li, Xiaoying ;
Wang, Wenjing ;
Zhang, Yan ;
Wang, Jin ;
Jiang, Xueyuan ;
Xiang, Yang ;
Xu, Chen ;
Zheng, Pingping ;
Zhang, Juanbin ;
Li, Ruiqiang ;
Zhang, Hongjie ;
Shang, Xiaobin ;
Gong, Ting ;
Ning, Guang ;
Wang, Jun ;
Zen, Ke ;
Zhang, Junfeng ;
Zhang, Chen-Yu .
CELL RESEARCH, 2008, 18 (10) :997-1006
[4]   Hepatocellular carcinoma: Recent trends in the United States [J].
El-Serag, HB .
GASTROENTEROLOGY, 2004, 127 (05) :S27-S34
[5]   miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting [J].
Esau, C ;
Davis, S ;
Murray, SF ;
Yu, XX ;
Pandey, SK ;
Pear, M ;
Watts, L ;
Booten, SL ;
Graham, M ;
McKay, R ;
Subramaniam, A ;
Propp, S ;
Lollo, BA ;
Freier, S ;
Bennett, CF ;
Bhanot, S ;
Monia, BP .
CELL METABOLISM, 2006, 3 (02) :87-98
[6]   Circulating nucleic acids (CNAs) and cancer - A survey [J].
Fleischhacker, M. ;
Schmidt, B. .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2007, 1775 (01) :181-232
[7]   An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling [J].
Fukao, Taro ;
Fukuda, Yoko ;
Kiga, Kotaro ;
Sharif, Jafar ;
Hino, Kimihiro ;
Enomoto, Yutaka ;
Kawamura, Aya ;
Nakamura, Kaito ;
Takeuchi, Tsutomu ;
Tanabe, Masanobu .
CELL, 2007, 129 (03) :617-631
[8]   Serum MicroRNAs Are Promising Novel Biomarkers [J].
Gilad, Shlomit ;
Meiri, Eti ;
Yogev, Yariv ;
Benjamin, Sima ;
Lebanony, Danit ;
Yerushalmi, Noga ;
Benjamin, Hila ;
Kushnir, Michal ;
Cholakh, Hila ;
Melamed, Nir ;
Bentwich, Zvi ;
Hod, Moshe ;
Goren, Yaron ;
Chajut, Ayelet .
PLOS ONE, 2008, 3 (09)
[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]   microRNA-122 stimulates translation of hepatitis C virus RNA [J].
Henke, Jura Inga ;
Goergen, Dagmar ;
Zheng, Junfeng ;
Song, Yutong ;
Schuettler, Christian G. ;
Fehr, Carmen ;
Juenemann, Christiane ;
Niepmann, Michael .
EMBO JOURNAL, 2008, 27 (24) :3300-3310