Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the fifth most common cancer overall. Late-stage therapeutic options are limited, while resection or ablation of small tumors can lead to overall survival rates of greater than 60 months. Therefore, early detection of HCC is crucial for patient survival. Currently, there are only three widely used biomarkers for HCC: α-fetoprotein (AFP), core fucosylated AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). All three of these markers have shown some value in the detection of HCC but with limited sensitivity. While serum is hepatic in nature, the tissue origin of these biomarkers is not determinable based on serum analysis alone, despite the ability of AFP to detect later-stage cancers. Therefore, further tissue analysis is needed for improved detection. Here, multi-omic approaches of HCC tissue are discussed, beginning with large-scale analyses to identify larger biocommunication networks predominant in HCC progression and moving toward smaller and more specific analyses. In the large-scale studies, the data suggests dysregulation in many major pathways, specifically the β-catenin/WNT and RAS pathways, and in specific sub-types, changes in specific genes such as TP53, TERT, and CTNNB1. Proteomics and glycomics are of special interest due to the glycosylation changes observed with AFP in HCC cases. From studying these glycomic and proteomic profiles of HCC serum and tissue, many groups have identified increased fucosylation and branching that are related to presence and progression of HCC. New techniques such as MALDI mass spectrometry glycan imaging have been used to identify specific glycan changes in cancer tissue. Further studies are necessary to accurately pinpoint the location of these modified glycoproteins to tumor-specific regions due to the heterogeneous composition of HCC tissue and to identify all the proteins that are modified and could act as potential biomarkers for HCC.
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