Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis

Abstract

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

Bioengineered Organoids Offer New Possibilities for Liver Cancer Studies: A Review of Key Milestones and Challenges

“…The clinical utility of biomarkers is still under discussion, largely due to their low sensitivity and specificity to HCC. Additionally, authors differ significantly regarding the cut-off points for assessing tumor progression with these biomarkers [29][30][31][32][33][34][35][36].…”

Midkine (MDK) in Hepatocellular Carcinoma: More than a Biomarker

“…Hence, several other molecules have been suggested as potent biomarkers for HCC diagnosis, as they are found to be dramatically elevated in HCC, including Dickkopf-1 (DKK-1), a secreted glycoprotein that antagonizes Wnt signaling, Golgi protein 73, a transmembrane glycoprotein of the Golgi complex, Glypican-3 (GPC3), a heparan sulphate proteoglycan, osteopontin (OPN), an integrin-binding glycophosphoprotein, des-gammacarboxy prothrombin (DCP), an abnormal prothrombin with impaired clotting function, and the enzyme gamma-glutamyl transferase (GGT), which is normally secreted by Kupffer cells and whose activity is greatly altered in HCC [10,11].…”

The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)

“…The non-metabolic causes of liver cell carcinogenesis relate to the intake of substances with mutagenic effects through diet, adversely affecting gene expression, and to engagement in a diet characterized by insufficient antioxidant potential [ 2 , 7 , 8 ]. As a result of these abnormalities, a diet lacking essential substances for detoxification and repair processes may promote the development of the cancer process [ 2 , 7 , 8 ].…”