MiRNA as a Diagnostic and Prognostic Biomarker of Hepatocellular Carcinoma

Background:

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third mortality rate of cancer in the world (Kamangar et al., 2006). Treatments of hepatocellular carcinoma include surgical resection, local therapies such as radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI), transarterial chemoembolization (TACE), and best supportive care(Bruix and Sherman, 2005). For patients who are not candidates for surgical intervention or local therapies, sorafenib is recommended (Cheng et al., 2009; Llovet et al., 2008). However, even after successful treatment such as surgical resection, most patients suffered from recurrence or progression of the tumor (Bruix and Sherman, 2005; Llovet et al., 2002; Llovet et al., 2008). Though there are several staging systems of HCC have been developed, such as the Okuda staging system, AJCC system, BCLC staging system, and CLIP scoring system, the prognostic value of each staging systems are not consistent(Chen et al., 2009), and applicability of each staging system depends on the treatment methodology selected.

Because of the shortcoming of clinical staging systems in predicting the outcome of HCC, it is of great interest to search serum biomarkers to predict the prognosis HCC (Fujiyama et al., 2002; Marrero and Lok, 2004). Among them, alpha-fetoprotein (AFP) is the mostly well-studied. AFP has been used as a marker in diagnosing HCC (Bruix et al., 2001) and as a prognostic factor for newly diagnosed HCC(1998). AFP is also of value as a predictive factor for chemotherapy response (Chan et al., 2009). However, the applicability of AFP for HCC after surgical resection of tumor or after local therapy is still uncertain. For patients with HCC and normal serum level of AFP, APF could not be used a prognostic factor. Other biomarkers, such as glipecan-3, are still under development (Marrero and Lok, 2004).

MicroRNAs (miRNAs), 17- to 25-nucleotide non-coding RNAs, are frequently dysregulated in cancer and emerging as novel non-invasive biomarker for cancer screening, diagnosis, monitor therapy efficacy and predict prognosis (Wu et al., 2007). MiRNAs are stably expression in serum as their resistance to endogenous RNase and easily storage with high stability (Aref et al., 2014). Several studies have shown abnormal expression of human serum miRNAs in many cancers such as liver, colorectal, and pancreatic cancer (Huang et al., 2010; Liu et al., 2012; Qi et al., 2013). The sensitivity of miRNA as a diagnostic biomarker of HCC could be up to 80% (Yin et al., 2014). Using miRNA arrays can generate miRNA signatures and further improve the sensitivity and specificity of biomarker for tumor diagnosis and prognosis prediction.

Trial purpose：