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An Insight Into the Role of Alpha-Fetoprotein (AFP) in the Development and Progression of Hepatocellular Carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is the primary malignancy of hepatocytes and the second most common cause of cancer-related mortality across the globe. Despite significant advancements in screening, diagnosis, and treatment modalities for HCC, the mortality-to-incidence ratio remain unacceptably high. A recent study indicates that a minor population of HCCs are AFP negative or express the normal range of AFP levels. Although it is a gold standard and a more reliable biomarker in the advanced stage of HCC and poorly differentiated tumors, it does not serve as a suitable means for screening HCC. AFP plays a significant role in the development and progression of HCC and understanding its role is crucial. By examining the molecular mechanisms involved in AFP-mediated tumorigenesis, we can better understand HCC pathogenesis and identify potential therapeutic targets. This article details the role of alpha-fetoprotein (AFP) in the carcinogenic transformation of hepatocytes. The article also focuses on information about the structure, biosynthesis, and regulation of AFP at the gene level. Additionally, it discusses the immune evasion, metastasis, and control of gene expression that AFP mediates during HCC.

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Data Availability

The authors confirm that the data supporting the findings of this study are available within the article.

Abbreviations

AFP:

Alpha-fetoprotein

AFPR:

Alpha-fetoprotein receptor

AKT:

Protein kinase B

AP-1:

Activator protein-1

ATRA:

All-trans retinoic acid

Bcl-2:

B-cell lymphoma 2

C/EBP:

CCAAT/enhancer-binding protein

CBP:

CREB-binding protein

CTLs:

Cytotoxic T lymphocytes

CXCL2:

CXC motif chemokine ligand 2

CXCR4:

CXC motif chemokine receptor 4

DC:

Dendritic cells

DCP:

Des carboxy prothrombin

E-cadherin:

Epithelial cadherin

ECM:

Extracellular matrix

EMT:

Epithelial–mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

Fam 20CKinase:

Family with sequence similarity 20, member C kinase

Fn14:

Fibroblast growth factor-inducible 14

Fox A:

Forkhead box A

FTF:

Four and a half LIM domain protein

GADD153:

Growth arrest and DNA damage-inducible protein 153

GADD45a:

Growth arrest and DNA damage-inducible protein 45 alpha

GRC:

Glucocorticoid receptor complex

HBV:

Hepatitis B virus

HBx:

Hepatitis B virus X protein

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HIF-1α:

Hypoxia-inducible factor 1-alpha

HNF:

Hepatocyte nuclear factor

IL-12:

Interleukin-12

K19:

Keratin 19

LCA:

Lens culinaris agglutinin

MAPK:

Mitogen-activated protein kinase.

MMP2/9:

Matrix Metalloproteinase 2/9

MPTP:

Mitochondrial Permeability Transition Pore

mRNA:

Messenger RNA

Mtor:

Mammalian target of rapamycin

N-cadherin:

Neural cadherin

NF-1:

Nuclear factor 1

NK cells:

Natural killer cells

N-ras:

Neuroblastoma RAS viral oncogene homolog

P21:

Cyclin-dependent kinase inhibitor 1

P53:

Tumor protein 53

PD-1:

Programmed cell death protein-1

PDL1:

Programmed Cell death-ligand 1

PI3K:

Phosphoinositide 3-kinase

PIP3:

Phosphatidylinositol (3,4,5)-trisphosphate

PTEN:

Phosphatase and tensin homolog

PTM:

Post-translational modification

RAR:

Retinoic acid receptor

RNAi:

RNA interference

siRNA:

Silencing RNA

SIRT1:

Sirtuin 1

Sp-1:

Specificity protein

TILs:

Tumor-infiltrating lymphocytes

TNFRSF12A:

Tumor necrosis factor receptor super family12A

TNM:

Tumor, node, metastasis staging system

TWEAK:

TNF-related weak inducer of apoptosis

US:

Ultra sound

ZBTB20:

Zinc finger and BTB domain-containing protein 20

Zhx2:

Zinc finger and homeoboxes protein 2

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Funding

We acknowledge the support of the Amrita Vishwa Vidyapeetham SEED grant [Project ID: K-PHAR-22-662] to LRN.

Author information

Author notes

  1. Swathy S. Samban, Aparna Hari, and Bhagyalakshmi Nair have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacognosy, Amrita School of Pharmacy, AIMS Health Science Campus, Amrita Vishwa Vidyapeetham, Ponekkara P.O., Kochi, Kerala, India

    Swathy S. Samban, Aparna Hari, Bhagyalakshmi Nair, Ayana. R. Kumar & Lekshmi R. Nath

  2. Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL, 32610, USA

    Benjamin S. Meyer & Vinod Vijayakurup

  3. Department of Gastroenterology and Hepatology, Amrita Institute of Medical Science, AIMS Health Science Campus, Ponekkara P.O., Kochi, Kerala, India

    Arun Valsan

Authors
  1. Swathy S. Samban
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  2. Aparna Hari
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  3. Bhagyalakshmi Nair
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  4. Ayana. R. Kumar
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  5. Benjamin S. Meyer
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  6. Arun Valsan
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  7. Vinod Vijayakurup
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  8. Lekshmi R. Nath
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Contributions

LRN & VV designed and conceptualized the review, writing and revising, and proofreading of the manuscript. SS & AH wrote the first draft. BLN, ARK, BSM, and AV conducted a literature survey and data collection. BLN carried out the artwork.

Corresponding authors

Correspondence to Vinod Vijayakurup or Lekshmi R. Nath.

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Samban, S.S., Hari, A., Nair, B. et al. An Insight Into the Role of Alpha-Fetoprotein (AFP) in the Development and Progression of Hepatocellular Carcinoma. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00890-0

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