Biomarkers in Diagnosis and Prediction of Hepatocellular Carcinoma Recurrence (Review)

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of death in oncological patients. The prognosis of the disease outcome depends directly on its timely detection. Currently, in the majority of countries, the diagnostic algorithm at the preclinical stage of tumor development includes determination of alpha-fetoprotein in combination with instrumental imaging techniques. This approach allows the detection of about 65-80% of liver tumors at an early stage (A according to the BCLC classification), whereas at a very early stage (0 according to the BCLC classification) only 32-50% of cases, the result which cannot be considered satisfactory. In this regard, the search for effective biomarkers of hepatocellular carcinoma is an important challenge that faces the world healthcare. Advances in proteomics and genomics have led to the discovery of numerous promising markers which are now being clinically tested. Molecules of protein nature proposed as hepatocellular carcinoma tumor markers in different periods of time are described in this review. Comparative data on their effectiveness and specificity are also presented. The possibility of isolated or combined use of these biomarkers for risk assessment and early diagnosis of primary liver cancer is considered.

Search for Effective Serum Tumor Markers for Early Diagnosis of Hepatocellular Carcinoma Associated with Hepatitis C

“…On the contrary, highly specific (>90%) protein markers (AFP-L3, plasminogen activator receptor (suPAR), DCP (PIVKA-II)) show low sensitivity of 28-76% [16,[22][23][24][25]. Thus, at present, no single tumor marker taken separately provides high diagnostic efficiency at the early stage of HCC [26].…”

“…As follows from individual publications and comprehensive reviews, the use of specific proteins such as ANXA2, MDK, α-1-fucosidase (AFU), and immune complex squamous cell carcinoma antigen — IgM (SCCA-IgM) allows reaching 80% of the sensitivity level. However, diagnostic specificity of detecting these tumor markers is rather low at high sensitivity and varies from 50.0 to 70.5% [ 16 , 19 – 22 ]. On the contrary, highly specific (>90%) protein markers (AFP-L3, plasminogen activator receptor (suPAR), DCP (PIVKA-II)) show low sensitivity of 28–76% [ 16 , 22 – 25 ].…”

“…However, diagnostic specificity of detecting these tumor markers is rather low at high sensitivity and varies from 50.0 to 70.5% [ 16 , 19 – 22 ]. On the contrary, highly specific (>90%) protein markers (AFP-L3, plasminogen activator receptor (suPAR), DCP (PIVKA-II)) show low sensitivity of 28–76% [ 16 , 22 – 25 ]. Thus, at present, no single tumor marker taken separately provides high diagnostic efficiency at the early stage of HCC [ 26 ].…”

“…For these reasons, the latest research has been directed towards the combined use of two, three, and even four tumor markers with different expression mechanisms in the process of carcinogenesis [ 27 – 30 ]. There have been described combinations including AFP, AFP-L3, DCP (PIVKA-II), ANXA2, OPN, DKK-1, receptor tyrosine kinase sAxl (AXL), thioredoxin (Trx1) [ 22 , 26 , 27 , 31 , 32 ]. In most cases, this provides the possibility to improve diagnostic efficiency in some way.…”

Longitudinal Circulating Levels of miR-23b-3p, miR-126-3p and lncRNA GAS5 in HCC Patients Treated with Sorafenib

“…Serum α-fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), and Dickkopf-1 (DKK1) proteins have already been described as circulating biomarkers of HCC. However, the use of AFP and DKK1 lack in sensitivity and reliability, while DCP amount reproducibility is controversial [34,35]. In order to meet the urgent need in the identification of predictive molecules to indicate responsiveness or resistance to sorafenib therapy, we set up a longitudinal study to analyze the circulating levels of different ncRNAs in patients treated with sorafenib.…”