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

Peng Qi,Chun-Fang Gao,Nan Li,Shu-Qun Cheng,Hao Wang,Yue-Feng Chen,Sunil K Ahuja

doi:10.1371/journal.pone.0028486

Abstract

BackgroundMicroRNAs (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 FindingsThis 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/SignificanceOur 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.

Highlights

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and it represents the third most common cause of death from cancer worldwide, with an increasing incidence expected in the decades [1]
Conclusions/Significance: Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of hepatocellular carcinoma (HCC) in healthy subjects, it might serve as a novel biomarker for liver injury but not for detection of HCC in chronic hepatitis B virus (HBV) infection patients
Patients, 48 chronic HBV infection patients without HCC, and 34 normal subjects were recruited into this study (Table 1)

Summary

Introduction

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and it represents the third most common cause of death from cancer worldwide, with an increasing incidence expected in the decades [1]. Biomarkers that can be sampled from body fluids, such as serum or urine, are desirable. Circulating nucleic acids (CNAs) are extracellular nucleic acids found in cell-free serum, plasma and other body fluids from healthy subjects as well as from patients. The ability to detect and quantitate specific DNA and RNA sequences has opened up the possibility of diagnosis and monitoring of diseases, especially in the field of cancer [5]. In some recent studies it has been suggested a kind of non-coding RNA— microRNA (miRNA), exist in cell-free serum and plasma, highlighting the field of using CNAs to diagnose cancer. MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for hepatocellular carcinoma (HCC)

Objectives

Methods

Results

Conclusion