Clinics and Research in Hepatology and Gastroenterology
Original articleEvaluation of miR-331-3p and miR-23b-3p as serum biomarkers for hepatitis c virus-related hepatocellular carcinoma at early stage
Introduction
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death in the world [1], [2]. Hepatitis C virus (HCV) infection in one of the main risk factors for developing HCC.
While great progress has been made in HCC treatment, the HCC prognosis remains poor and side effects of chemotherapy in patients are common [1]. The result of treatment depends on the HCC stage at the time of diagnosis. Early treatment of HCC can greatly improve life expectancy and reduce mortality. Although alpha-fetoprotein (AFP) serves as the most widely used marker for screening HCC patients, its sensitivity is quite low [3], [4], which is not sufficient for accurate diagnosis. Therefore new tumor markers to complement AFP to distinguish the early stage of HCC from risk persons are urgently needed.
MicroRNAs (miRNAs) are small, noncoding regulatory RNAs, involved in various biological processes including proliferation, differentiation and apoptosis [5]. It is well established that miRNAs may act as tumor suppressors, oncogenes, or even possess a dual nature playing both roles depending on the cellular needs in tumor occurrence and development [6], [7]. Most miRNAs can be released to blood and miRNAs are stable in plasma or serum [8]. As such, circulating miRNAs have been proposed to be promising biomarkers for noninvasive diagnosis and monitoring of tumors including HCC [8], [9], [10], [11], [12].
MiR-331-3p is one of the most commonly upregulated miRNAs that promote proliferation, migration and invasion of the tumor cells, including pancreatic tumor, breast tumor and HCC [13], [14], [15]. MiR-23b-3p is a down-regulated miRNA in the tumor, suppressing tumor cells proliferation and migration [16], [17], [18]. Recent studies showed miR-331-3p and miR-23b-3p were aberrantly expressed in HCC tissues [13], [17], and our previous screened study also found miR-331-3p and miR-23b-3p were differently expressed in the serum of HCC patients versus liver cirrhosis controls. However, the values of miR-331-3p and miR-23b-3p in serum for diagnosis of HCC have not been fully evaluated. The aim of this study was to investigate the values of serum miR-331-3p and miR-23b-3p as potential biomarkers in the screening of HCV-related HCC at early stage and their relationships with liver fibrosis.
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Patients
The study included 146 HCV-infected patients; 40 patients with early-stage HCC and 106 non-malignant HCV-associated chronic liver disease (CLD) patients, who were recruited from our institution during the study period. The study protocol and informed consent were approved by the ethics committee of the Affiliated Hospital of Chengde Medical University. All the patients were positive for HCV-RNA in sera for more than 6 months. All HCC patients were on top of HCV cirrhosis and were confirmed by
Characteristics of the study subjects
The demographic and pathologic features of the studied participants are shown in Table 1. Subjects were categorized into 5 groups; Health control (HC), no fibrosis group (F0), mild fibrosis group (F1 + F2), and severe fibrosis/cirrhosis group (F3 + F4) and HCC group. As showed by the table, there was a significant difference between the diseased groups regarding age (P < 0.001). Regarding gender, although males were predominant in HCV related liver disease, there was no statistically different
Discussion
Chronic HCV infection usually results in the development of LC and later HCC. In China, the number of individuals infected with HCV is increasing year by year [1]. Early diagnosis of HCC among high-risk patients is important to reduce the mortality of the disease. Currently, serum AFP has mainly been used in the clinic for diagnosis of HCC. However, its sensitivity and specificity are not satisfying [3], [4]. Discovery of new and more sensitive biomarkers for early detection of HCC is of very
Conclusions
Our results indicate that serum miR-331-3p and miR-23b-3p expressed aberrantly in the patients with HCV-related HCC at early stage and are potential biomarkers to complement AFP. The combination of miR-331-3p, miR-23b-3p and AFP could increase the diagnostic performance and may provide a new diagnostic strategy for the diagnosis of early-stage HCC from high-risk patients. Our findings need to be confirmed by replication studies with larger number of samples, especially in other ethnic
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Contributors
QS, JL and BJ were responsible for the conception and design of the study. All authors were responsible for acquisition and analysis of data; furthermore, QS, JL, BJ and TW were in charge of statistical analysis. QS and JL drafted the manuscript; QS, JL, BJ TW and JG revised and commented on the draft, and all authors read and approved the final version of the manuscript.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgment
None.
References (30)
- et al.
Primary liver cancer: worldwide incidence and trends
Gastroenterology
(2004) - et al.
Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis
J Hepatol
(1994) MicroRNAs
Cell
(2004)- et al.
A comprehensive clinicopathological evaluation of the differential expression of microRNA-331 in breast tumors and its diagnostic significance
Clin Biochem
(2018) - et al.
microRNA-23b suppresses epithelial-mesenchymal transition (EMT) and metastasis in hepatocellular carcinoma via targeting Pyk2
Biomed Pharmacother
(2017) - et al.
Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method
Methods
(2001) - et al.
Circulating microRNAs panel as a diagnostic tool for discrimination of HCV-associated hepatocellular carcinoma
Clin Res Hepatol Gastroenterol
(2017) - et al.
Hepatocellular carcinoma in the Asia pacific region
J Gastroenterol Hepatol
(2009) - et al.
Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period
Clin Mol Hepatol
(2012) - et al.
Integrated analysis of differentially expressed mRNAs and miRNAs between hepatocellular carcinoma and their matched adjacent normal liver tissues
Oncol Rep
(2015)
Oncomirs – microRNAs with a role in cancer
Nat Rev Cancer
Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases
Cell Res
A Circulating MicroRNA Signature as a Biomarker for Prostate Cancer in a High Risk Group
J Clin Med
A five-microRNA panel in plasma was identified as potential biomarker for early detection of gastric cancer
Br J Cancer
Circulating microRNAs as stable blood-based markers for cancer detection
Proc National Acad Sci U S A
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These authors contributed equally to this work and should be considered co-first authors.