The Emerging Influences of Alpha-Fetoprotein in the Tumorigenesis and Progression of Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma is characterized by aggressive invasion, rapid progress and poor prognosis. Since hepatocellular carcinoma is a highly heterogeneous cancer, both at the molecular and histological level, the precision medicine for patients is not very effective and the systematic targeted therapies remain unsatisfactory. The identification of new targets and molecular pathways is urgently needed for drug treatment of hepatocellular carcinoma. Alpha-fetoprotein acts as the most common tumor marker used for hepatocellular carcinoma diagnosis. Alpha-fetoprotein in serum and cytoplasm shows very different influences in the tumorigenesis and progression of hepatocellular carcinoma. The aim of this review is to summarize the current knowledge of the role of alpha-fetoprotein in hepatocellular carcinoma. ABSTRACT: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, and its mortality rate is the third-highest, after lung cancer and colorectal cancer. Currently, systematic targeted therapies for HCC mainly include multiple kinase inhibitors and immunotherapy. However, these drugs carry a black-box warning about the potential for inducing severe toxicity, and they do not significantly prolong the survival period of patients due to the highly heterogeneous characteristics of HCC etiology. In order to improve the prediction, effective treatment and prognosis of HCC, the tools and different biomarkers in clinical practices are recommended. Alpha-fetoprotein (AFP) is the earliest and the most widely used serum marker in the detection of HCC. Interestingly, serum AFP and cytoplasmic AFP show different, even opposite, roles in the cancer progression of HCC. This review focuses on biological characteristics, regulatory mechanisms for gene expression, emerging influences of AFP in HCC and its possible implications in HCC-targeted therapy.