Abstract
Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease.
Highlights
The serum concentration of AFP is the most commonly used marker for early diagnosis, monitoring and recurrence of Hepatocellular carcinoma (HCC), albeit its sensitivity is around 40%: most tumors do not produce AFP at all or only in advanced stages and on the other hand, elevation of AFP is found in patients with chronic liver diseases or acute viral hepatitis too
This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease
MiRNAs participate in various processes such as HCC proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, angiogenesis and drug resistance
Summary
With an estimated incidence of >1 million cases by 2025, is the fourth leading cause of cancer-related deaths worldwide, making it a global health challenge [1]. Hepatocellular carcinoma (HCC) is the dominant type of liver cancer, accounting for approximately 80% of all liver cancers [2]. Despite the incidence rates are decreasing in some high-rate areas, primary liver cancer remains the second-most common cause of cancer mortality in many low-rate areas [3]. Infection are the most prominent risk factors for hepatocarcinogenesis, alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), associated with diabetes mellitus or metabolic syndrome, are becoming the leading etiology of HCC, in the West [5,6,7]. HCC therapy, the 5-year survival rate for late-stage HCC remains poor, because of its late diagnosis, resistance to therapy and high frequency of recurrence [8]
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