Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

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 significa...

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Published in:Liver international Vol. 39; no. 12; pp. 2214 - 2229
Main Authors: Galle, Peter R., Foerster, Friedrich, Kudo, Masatoshi, Chan, Stephen L., Llovet, Josep M., Qin, Shukui, Schelman, William R., Chintharlapalli, Sudhakar, Abada, Paolo B., Sherman, Morris, Zhu, Andrew X.
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01.12.2019
Subjects:
alpha-Fetoproteins - metabolism
alpha‐fetoprotein
Angiogenesis
Antigens
Antigens, Neoplasm - blood
Biomarkers
Biomarkers - blood
Cancer
Carcinoma, Hepatocellular - blood
Gene expression
Growth factors
Hepatocellular carcinoma
Humans
Liver cancer
Liver Neoplasms - blood
Medical treatment
Pathogenesis
Proteins
Risk analysis
Risk factors
Tumors
Vascular endothelial growth factor
biomarkers
hepatocellular carcinoma
alpha-fetoprotein
ISSN:1478-3223, 1478-3231, 1478-3231
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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 the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.
AbstractList 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 the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.
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 the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.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 the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.
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 the historical and current uses of AFP for screening and surveillance, diagnosis, its utility as a prognostic and predictive biomarker and its role as a tumour antigen in HCC. Taken together, these data demonstrate the relevance of AFP for patients with HCC and identify several remaining questions that will benefit from future research.
Author Sherman, Morris
Chintharlapalli, Sudhakar
Zhu, Andrew X.
Galle, Peter R.
Chan, Stephen L.
Schelman, William R.
Foerster, Friedrich
Kudo, Masatoshi
Qin, Shukui
Abada, Paolo B.
Llovet, Josep M.
Author_xml – sequence: 1
  givenname: Peter R.
  orcidid: 0000-0001-8294-0992
  surname: Galle
  fullname: Galle, Peter R.
  email: Peter.Galle@unimedizin-mainz.de
  organization: University Medical Center of the Johannes Gutenberg University Mainz
– sequence: 2
  givenname: Friedrich
  orcidid: 0000-0002-3234-8891
  surname: Foerster
  fullname: Foerster, Friedrich
  organization: University Medical Center of the Johannes Gutenberg University Mainz
– sequence: 3
  givenname: Masatoshi
  surname: Kudo
  fullname: Kudo, Masatoshi
  organization: Kindai University
– sequence: 4
  givenname: Stephen L.
  surname: Chan
  fullname: Chan, Stephen L.
  organization: Chinese University of Hong Kong
– sequence: 5
  givenname: Josep M.
  surname: Llovet
  fullname: Llovet, Josep M.
  organization: Institució Catalana de Recerca i Estudis Avançats (ICREA)
– sequence: 6
  givenname: Shukui
  surname: Qin
  fullname: Qin, Shukui
  organization: Nanjing Chinese Medicine University
– sequence: 7
  givenname: William R.
  surname: Schelman
  fullname: Schelman, William R.
  organization: Eli Lilly and Company
– sequence: 8
  givenname: Sudhakar
  surname: Chintharlapalli
  fullname: Chintharlapalli, Sudhakar
  organization: Eli Lilly and Company
– sequence: 9
  givenname: Paolo B.
  surname: Abada
  fullname: Abada, Paolo B.
  organization: Eli Lilly and Company
– sequence: 10
  givenname: Morris
  surname: Sherman
  fullname: Sherman, Morris
  organization: Toronto General Hospital
– sequence: 11
  givenname: Andrew X.
  surname: Zhu
  fullname: Zhu, Andrew X.
  organization: Harvard Medical Center
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31436873$$D View this record in MEDLINE/PubMed
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Issue 12
Keywords biomarkers
hepatocellular carcinoma
alpha-fetoprotein
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Snippet 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...
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...
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SubjectTerms alpha-Fetoproteins - metabolism
alpha‐fetoprotein
Angiogenesis
Antigens
Antigens, Neoplasm - blood
Biomarkers
Biomarkers - blood
Cancer
Carcinoma, Hepatocellular - blood
Gene expression
Growth factors
Hepatocellular carcinoma
Humans
Liver cancer
Liver Neoplasms - blood
Medical treatment
Pathogenesis
Proteins
Risk analysis
Risk factors
Tumors
Vascular endothelial growth factor
Title Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fliv.14223
https://www.ncbi.nlm.nih.gov/pubmed/31436873
https://www.proquest.com/docview/2319103918
https://www.proquest.com/docview/2288736107
Volume 39
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