West Connor A., Black Alyson P., Mehta Anand S.
Department of Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA
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 , , and . 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.
肝细胞癌（HCC）是最常见的肝癌类型，也是全球第五大常见癌症。晚期治疗选择有限，而小肿瘤的切除或消融可使总生存率超过60个月。因此，HCC的早期检测对患者生存至关重要。目前，HCC仅有三种广泛使用的生物标志物：甲胎蛋白（AFP）、核心岩藻糖基化甲胎蛋白（AFP-L3）和异常凝血酶原（DCP）。这三种标志物在HCC检测中均显示出一定价值，但敏感性有限。虽然血清本质上是肝脏来源的，但仅基于血清分析无法确定这些生物标志物的组织来源，尽管AFP能够检测晚期癌症。因此，需要进一步的组织分析以提高检测效果。在此，将讨论HCC组织的多组学方法，首先从大规模分析开始，以识别在HCC进展中占主导地位的更大生物通讯网络，然后转向更小、更具体的分析。在大规模研究中，数据表明许多主要通路存在失调，特别是β-连环蛋白/ WNT和RAS通路，并且在特定亚型中，特定基因如[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]发生了变化。由于在HCC病例中观察到AFP的糖基化变化，蛋白质组学和糖组学备受关注。通过研究HCC血清和组织的这些糖组学和蛋白质组学特征，许多研究小组已经确定了与HCC的存在和进展相关的岩藻糖基化增加和分支增加。诸如基质辅助激光解吸电离质谱聚糖成像等新技术已被用于识别癌组织中的特定聚糖变化。由于HCC组织成分的异质性，需要进一步研究以准确确定这些修饰糖蛋白在肿瘤特异性区域的位置，并识别所有被修饰且可作为HCC潜在生物标志物的蛋白质。
