Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally due, in part, to the majority of patients being diagnosed with intermediate or advanced stage disease. Our increased understanding of the heterogeneous molecular pathogenesis of HCC has led to significant developments in novel targeted therapies. Despite these advances, there remains a high unmet need for new treatment options. HCC is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker.In fact, numerous biomarkers have been studied in HCC, but alpha-fetoprotein (AFP) remains the most widely used and accepted serum marker since its discovery over 60 years ago. This review summarizes the most relevant studies associated with the regulation of AFP at the gene and protein levels; the pathophysiology of AFP as a pro-proliferative protein; and the correlation of AFP with molecular HCC subclasses, the vascular endothelial growth factor pathway and angiogenesis. Also described are | 2215 GALLE Et AL.

<p>A Novel Prognostic Scoring Model Based on Albumin and γ-Glutamyltransferase for Hepatocellular Carcinoma Prognosis</p>

“…5 Alpha-fetoprotein (AFP), one of the first protein tumor markers, has been widely used and accepted since its discovery > 60 years ago. 6,7 However, it has low sensitivity and specificity in predicting the prognosis of HCC and has no diagnostic value in small HCCs. 8 The tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Okuda staging systems have been commonly used in stratifying and assessing the prognosis of HCC.…”

Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit

“…Alpha-fetoprotein (AFP), a secreted 70 kD glycoprotein, has been used as a biomarker for HCC as elevated expression of AFP in tumors and serum is found in 60-80% of HCC patients and correlates with poor prognosis (13). AFP is commonly expressed in the fetal liver and yolk sac during the first trimester of pregnancy, but declines sharply after birth and remains low in adulthood (13).…”

“…Alpha-fetoprotein (AFP), a secreted 70 kD glycoprotein, has been used as a biomarker for HCC as elevated expression of AFP in tumors and serum is found in 60-80% of HCC patients and correlates with poor prognosis (13). AFP is commonly expressed in the fetal liver and yolk sac during the first trimester of pregnancy, but declines sharply after birth and remains low in adulthood (13). While vital for the developing fetus, the role of AFP in adult tissues is less well-understood but appears dispensable, thus making it a promising tumor antigen for T cell-based immunotherapies (13).…”

“…AFP is commonly expressed in the fetal liver and yolk sac during the first trimester of pregnancy, but declines sharply after birth and remains low in adulthood (13). While vital for the developing fetus, the role of AFP in adult tissues is less well-understood but appears dispensable, thus making it a promising tumor antigen for T cell-based immunotherapies (13). A human TCR specific for AFP 158−166 was recently identified from healthy donors, but the antitumor effect is restricted, probably due to its low affinity (14).…”

Adherence and quality are key for a beneficial HCC surveillance

“…US is an inexpensive, non-invasive, and highly available surveillance method recommended by the most relevant scientific societies involved the in HCC management. [3][4][5] Undoubtedly, the detection of HCC by US in a cirrhotic liver might be limited by several factors, including coarse liver parenchyma that difficult nodule detection, the increasingly frequent obesity as a main driver of cirrhosis in Western countries associated to inadequate ultrasound beam penetration, 13 15,16 Given the widespread use of US, large-scale randomized controlled trials in developed countries aimed to confirm the benefit of HCC surveillance in terms of survival are largely impractical due to ethical concerns in randomizing patients at risk for HCC to a no-intervention group and the sheer difficulty of including subjects after informed consent of the potential benefits/risks is requested. 17 For that reason, studies as the one reported by Chen et al 9 showing the benefits of surveillance are very supportive, and call the attention for the operator dependency of US, the importance of high-quality training and performance and the urgent need of broader adherence and adoption of guidelines.…”