**1. Introduction**

Hepatocarcinoma, also termed as hepatocellular carcinoma (HCC) or liver carcinoma, is the most common primary liver malignant disease in adults [1]. One of the most striking features of this malignant tumor is the wide variation in its incidence in different parts of the world. In areas of high incidence, such as China, hepatocarcinoma is among the leading cause of cancer-correlated deaths in recent years, with an annual incidence of approximately 40 per 100,000 [2, 3]. However, the countries in the low incidence, such as the USA, have only 2.3% of cancer-related deaths in

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

past decades. Globally, hepatocarcinoma is the fifth most common cancer among males and the eighth most common among females [1]. Furthermore, the incidence of this tumor generally increases with age, although there are geographic and gender differences. The precise reasons for this difference is not known, but growing evidence has exhibited that multiple factors including chronic viral hepatitis B (HBV) and C (HCV), aflatoxin (such as aflatoxin B1) exposure, hepatic cirrhosis, obesity, diabetes, and vitamin D deficiency play an important role [4–6]. Although the molecular mechanism of hepatocarcinoma has been unclear, these hepatocarcinoma patients with early diagnosis often have good prognosis with more than 50% of five overall survival rate [6]. This is mainly because they benefit from the curative treatment such as curative resection and orthotropic liver transplantation [6]. However, if patients are lately diagnosed, the cumulative 5-year survival rate remarkably reduces to less than 10%, and tumor recurrence risk noticeably increases (about 70–80% of 5-year recurrence rate). Thus, it is very urgent to identify specific and sensitive markers for early diagnosing hepatocarcinoma at a curative stage, monitoring recurrence of tumor, and predicting prognosis of tumor [6].

single-stranded RNA typically consisting of 18–24 nucleotides. Originally, they are first transcribed by the RNA polymerase enzyme II into a kind of primary production named as primary microRNA that is characterized by long nucleotide sequences, 5′-cap structure, and 3′-poly-A tail, resembling protein-coding mRNAs. Then, primary microRNAs form a hairpin-shaped stemloop structure and are processed into microRNA precursors (usually containing 60–70 nucleotides) by the microprocessor complex (consisting of DGCR8/Pasha and Drosha). After that, their precursors are transported to the cytoplasm and treated into a short double-strand duplex structure by another RNase endonuclease III (also called Dicer). Finally, the duplex structure (also called microRNA-microRNA\*) is unwound into mature microRNAs by helicases. To date, it has been identified that there are more than 1800 microRNAs in the mammalian genome (miRDatabase) (**Figure 1**) [30]. Functionally, microRNAs are involved in regulating the expression of their

The Diagnostic and Prognostic Potential of MicroRNAs for Hepatocellular Carcinoma

http://dx.doi.org/10.5772/intechopen.72276

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**Figure 1.** Biosynthesis and functions of microRNA. In the nucleus, the microRNA genes are transcribed into primary microRNAs by RNA polymerase II (Pol II). The primary microRNAs are then cleaved by Drosha and DGCR8 and produce their precursor molecules (also named as precursor microRNA). After that, the precursor molecules are transported to the cytoplasm by Exportin-5 and Ran-GTP and undergo final processing step including the cleavage by Dicer and the formation of stem-loop duplex molecule structure which contains the single-stranded mature microRNA molecule and a microRNA\* fragment. Finally, the duplex molecule structure is incorporated into the RNA-induced silencing complex (RISC), the microRNA\* fragments are degraded, and mature microRNA molecules are formed. The mature microRNAs can display genic regulation role via recognizing and binding to the 3′-untranslated region of their

target genes' mRNAs. *Note*: This figure is plotted according to ScienceSlides (version#2016).

Currently, the early diagnosis of hepatocarcinoma is based on the following two classes of methods: imaging examination which mainly consists of ultrasonography, magnetic resonance imaging, and computed tomography and serological tests such as serous α-fetoprotein (AFP) [4, 7]. Although advances in imaging technologies have significantly improved the early screening of hepatocarcinoma, these methods are so costly and unsatisfactory in early diagnosis that is not suitable for daily clinical practice [4, 7]. About serological methods, AFP is the most widely utilized marker for the diagnosis and prognosis prediction of hepatocarcinoma. However, this biomarker is limited because of its modest accuracy (with sensitivity of 40–65% and specificity of 87–96%) and about 30–40% of the false-negative rate for patients with early-stage hepatocarcinoma [8]. Additionally, serum AFP levels of some benign hepatic lesions, such as liver nodular hyperplasia, inflammation lesions of liver, and liver fibrotic cirrhosis, may give false-positive results [8]. Therefore, the reliability of this biomarker to determine hepatocarcinoma is inadequate because of its low sensitivity and specificity.

Emerging evidence has exhibited a correlation between dysregulation of microRNAs and development of hepatocarcinoma. Particularly, microRNAs are characterized by high stability in body fluids (including the blood and urine) and tissue specific in expression patterns, indicative of microRNAs in body fluids acting as potentially novel and ideal biomarkers for hepatocarcinoma diagnosis and prognosis prediction [8–16].

This review attempts to briefly review currently available data on microRNAs and hepatocarcinoma, with emphasis on (1) the biogenesis and function of microRNA, (2) potential diagnostic and prognostic value for hepatocarcinoma, and (3) the different value for hepatocarcinoma induced by different causes. Additionally, we summarized the clinical applicative perspectives and potential challenges of microRNAs in hepatocarcinoma.
