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World Journal of Gastroenterology Jan 2022Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other... (Review)
Review
Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; alpha-Fetoproteins
PubMed: 35110946
DOI: 10.3748/wjg.v28.i2.216 -
Therapeutic Delivery Jan 2019
Topics: Clinical Trials, Phase I as Topic; Humans; Myeloid-Derived Suppressor Cells; Neoplasms; Receptors, Peptide; Teratogens; Toxins, Biological; Treatment Outcome; alpha-Fetoproteins
PubMed: 30730821
DOI: 10.4155/tde-2018-0068 -
Trends in Immunology Jun 2022α-Fetoprotein (AFP) is a fetal glycoprotein produced by most human hepatocellular carcinoma tumors. Research has focused on its immunosuppressive properties in... (Review)
Review
α-Fetoprotein (AFP) is a fetal glycoprotein produced by most human hepatocellular carcinoma tumors. Research has focused on its immunosuppressive properties in pregnancy, autoimmunity, and cancer, and human AFP directly limits the viability and functionality of human natural killer (NK) cells, monocytes, and dendritic cells (DCs). AFP-altered DCs can promote the differentiation of naïve T cells into regulatory T cells. These properties may work to shield tumors from the immune system. Recent efforts to define the molecular characteristics of AFP identified key structural immunoregulatory domains and bioactive roles of AFP-bound ligands in immunomodulation. We propose that a key mechanism of AFP immunomodulation skews DC function through cellular metabolism. Delineating differences between fetal 'normal' AFP (nAFP) and tumor-derived AFP (tAFP) has uncovered a novel role for tAFP in altering metabolism via lipid-binding partners.
Topics: Carcinoma, Hepatocellular; Dendritic Cells; Female; Humans; Immunomodulation; Liver Neoplasms; Pregnancy; alpha-Fetoproteins
PubMed: 35550875
DOI: 10.1016/j.it.2022.04.001 -
Pathology Oncology Research : POR Apr 2020Hepatocellular carcinoma (HCC) is one of the most malignant cancer with high morbidity and mortality which lead to a serious burden to society. AFP (alpha-fetoprotein)... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most malignant cancer with high morbidity and mortality which lead to a serious burden to society. AFP (alpha-fetoprotein) is the most widely used serum biomarker to detect HCC worldwide. However, no AFP elevation have been found in many HCC and AFP analysis can't be used to screen HCC in these cases. Currently, many studies have been carried out to find reliable biomarker in diagnosing AFP-negative HCC. Such biomarker would help the diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. In this review, we highlight the important role of biomarkers that can differentiate AFP-negative HCCs, and discuss their potential clinical applications as biomarkers for the diagnosis of AFP-negative HCC.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Early Diagnosis; Humans; Liver Neoplasms; alpha-Fetoproteins
PubMed: 30661224
DOI: 10.1007/s12253-019-00585-5 -
Canadian Journal of Gastroenterology &... 2018Hepatocarcinoma is one of the most prevalent gastroenterological cancers in the world with less effective therapy. As an oncofetal antigen and diagnostic marker for... (Review)
Review
Hepatocarcinoma is one of the most prevalent gastroenterological cancers in the world with less effective therapy. As an oncofetal antigen and diagnostic marker for liver cancer, alpha-fetoprotein (AFP) possesses a variety of biological functions. Except for its diagnosis in liver cancer, AFP has become a target for liver cancer immunotherapy. Although the immunogenicity of AFP is weak and it could induce the immune escapes through inhibiting the function of dendritic cells, natural killer cells, and T lymphocytes, AFP has attracted more attention in liver cancer immunotherapy. By in vitro modification, the immunogenicity and immune response of AFP could be enhanced. AFP-modified immune cell vaccine or peptide vaccine has displayed the specific antitumor immunity against AFP-positive tumor cells and laid a better foundation for the immunotherapy of liver cancer.
Topics: Animals; Cancer Vaccines; Carcinoma, Hepatocellular; Humans; Immunotherapy; Liver Neoplasms; Tumor Escape; alpha-Fetoproteins
PubMed: 29805966
DOI: 10.1155/2018/9049252 -
Biosensors Sep 2022Alpha-fetoprotein (AFP) is widely-known as the most commonly used protein biomarker for liver cancer diagnosis at the early stage. Therefore, developing the highly... (Review)
Review
Alpha-fetoprotein (AFP) is widely-known as the most commonly used protein biomarker for liver cancer diagnosis at the early stage. Therefore, developing the highly sensitive and reliable method of AFP detection is of essential demand for practical applications. Herein, two types of aptamer-based AFP detection methods, i.e., optical and electrochemical biosensors, are reviewed in detail. The optical biosensors include Raman spectroscopy, dual-polarization interferometry, resonance light-scattering, fluorescence, and chemiluminescence. The electrochemical biosensors include cyclic voltammetry, electrochemical impedance spectroscopy, and giant magnetic impedance. Looking into the future, methods for AFP detection that are high sensitivity, long-term stability, low cost, and operation convenience will continue to be developed.
Topics: alpha-Fetoproteins; Electrochemical Techniques; Limit of Detection; Biosensing Techniques; Aptamers, Nucleotide
PubMed: 36290918
DOI: 10.3390/bios12100780 -
The Journal of Clinical Investigation Jun 2023Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is...
Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is an attractive alternative approach to immunotherapy. However, its efficacy remains insufficiently evaluated in preclinical studies. Here, we investigated HCC-associated self/tumor antigen, α-fetoprotein-based (AFP-based) vaccine immunization for treating AFP (+) HCC mouse models. We found that AFP immunization effectively induced AFP-specific CD8+ T cells in vivo. However, these CD8+ T cells expressed exhaustion markers, including PD1, LAG3, and Tim3. Furthermore, the AFP vaccine effectively prevented c-MYC/Mcl1 HCC initiation when administered before tumor formation, while it was ineffective against full-blown c-MYC/Mcl1 tumors. Similarly, anti-PD1 and anti-PD-L1 monotherapy showed no efficacy in this murine HCC model. In striking contrast, AFP immunization combined with anti-PD-L1 treatment triggered significant inhibition of HCC progression in most liver tumor nodules, while in combination with anti-PD1, it induced slower tumor progression. Mechanistically, we demonstrated that HCC-intrinsic PD-L1 expression was the primary target of anti-PD-L1 in this combination therapy. Notably, the combination therapy had a similar therapeutic effect in the cMet/β-catenin mouse HCC model. These findings suggest that combining the AFP vaccine and immune checkpoint inhibitors may be effective for AFP (+) HCC treatment.
Topics: Mice; Animals; Carcinoma, Hepatocellular; Liver Neoplasms; Immune Checkpoint Inhibitors; alpha-Fetoproteins; Myeloid Cell Leukemia Sequence 1 Protein; CD8-Positive T-Lymphocytes; Cancer Vaccines
PubMed: 37040183
DOI: 10.1172/JCI163291 -
Single-cell characteristics and malignancy regulation of alpha-fetoprotein-producing gastric cancer.Cancer Medicine May 2023To characterize alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) at the single-cell level and to identify regulatory factors for AFP expression and malignancy.
OBJECTIVE
To characterize alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) at the single-cell level and to identify regulatory factors for AFP expression and malignancy.
METHODS
ScRNA-seq was performed on two tumors collected from patients with AFPGC. InferCNV and sub-clustering were applied to identify typical AFPGC cells, followed by AddModuleScore, pathway enrichment, Pseudo-time, and Scenic analyses. Data from a gastric cancer (GC) cohort were collected for conjoint analysis. The analytical results were verified by cell experiments and immunohistochemistry.
RESULTS
AFPGC cells are similar to hepatocytes in transcriptome and transcriptional regulation, with kinetic malignancy-related pathways, compared to the common malignant epithelium. In addition, compared to common GC cells, malignancy-related pathways, such as epithelial-mesenchymal transition (EMT) and angiogenesis, were upregulated in AFPGC. Mechanistically, Dickkopf-1 (DKK1) was found to be associated with AFP expression and malignant phenotype upon combining our scRNA-seq data with a public database, which was further verified by a series of in vitro experiments and immunohistochemistry.
CONCLUSION
We demonstrated the single-cell characteristics of AFPGC and that DKK1 facilitates AFP expression and malignancy.
Topics: Humans; Stomach Neoplasms; alpha-Fetoproteins; Prognosis
PubMed: 37017469
DOI: 10.1002/cam4.5883 -
Frontiers in Immunology 2023Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains...
Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In the present study, we explored the correlation between AFP regulation of macrophage function and the possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) and monocytes from healthy donors were used to analyze the effect of AFP on the macrophages' phenotype and phagocytosis. THP-1 cells and healthy human donor-derived monocytes were polarized into M0 macrophages induced by phorbol ester (PMA), and M0 macrophages were polarized into M1 macrophages induced by lipopolysaccharide(LPS) and interferon-γ(IFN-γ). Interleukin-4(IL-4) and interleukin-13(IL-13) were used to induce M0 macrophage polarization into M2 macrophages. Tumor-derived AFP(tAFP) stimulated M0 macrophage polarization into M2 macrophages and inhibited M1 macrophages to phagocytize HCC cells. The role of AFP in promoting macrophage polarization into M2 macrophages and inhibiting the M1 macrophages to phagocytize HCC cells may be involved in activating the PI3K/Akt signaling pathway. AFP could also enhanced the migration ability of macrophages and inhibited the apoptosis of HCC cells when co-cultured with M1-like macrophages. AFP is a pivotal cytokine that inhibits macrophages to phagocytize HCC cells.
Topics: Humans; alpha-Fetoproteins; Carcinoma, Hepatocellular; Phosphatidylinositol 3-Kinases; Liver Neoplasms; Macrophages; Interferon-gamma; Phenotype
PubMed: 36911723
DOI: 10.3389/fimmu.2023.1081572 -
World Journal of Surgical Oncology Oct 2022The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high...
BACKGROUND
The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy.
METHODS
The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan-Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis.
RESULTS
The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS.
CONCLUSION
The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Hepatectomy; CA-19-9 Antigen; Prognosis; Liver Neoplasms; Retrospective Studies; Aspartate Aminotransferases; Carbohydrates
PubMed: 36258212
DOI: 10.1186/s12957-022-02806-9