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Methods in Molecular Biology (Clifton,... 2023Hepatocellular carcinoma (HCC) is one of the most deadly neoplasms with a poor prognosis. Due to the significant tumor heterogeneity of HCC, alpha-fetoprotein (AFP) or... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most deadly neoplasms with a poor prognosis. Due to the significant tumor heterogeneity of HCC, alpha-fetoprotein (AFP) or liver biopsy has not yet met the clinical needs in terms of early diagnosis or determining prognosis. In recent years, liquid biopsy techniques that analyze tumor by-products released into the circulation have shown great potential. Its ability to monitor tumors in real time and respond to their global characteristics is expected to improve the management of HCC patients clinically. This review discusses some of the findings of a liquid biopsy in terms of diagnosis and prognosis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Liquid Biopsy; Biomarkers, Tumor
PubMed: 37450121
DOI: 10.1007/978-1-0716-3346-5_14 -
Drugs Feb 2020Ramucirumab (Cyramza), a fully human anti-VEGFR-2 monoclonal antibody, has been approved as monotherapy for the treatment of patients with hepatocellular carcinoma (HCC)... (Review)
Review
Ramucirumab (Cyramza), a fully human anti-VEGFR-2 monoclonal antibody, has been approved as monotherapy for the treatment of patients with hepatocellular carcinoma (HCC) and α-fetoprotein levels ≥ 400 ng/mL who have been treated with sorafenib. Ramucirumab significantly prolonged overall survival (OS) and progression-free survival (PFS) relative to placebo in this population in the randomized, double-blind phase 3 REACH 2 trial. These benefits were seen in key prespecified subgroups based on demographic and disease characteristics. Ramucirumab had an acceptable tolerability profile and manageable safety profile in these patients, with the majority of treatment-related adverse events being mild or moderate in severity. The safety profile of ramucirumab was consistent with that expected for agents targeting the VEGF/VEGFR axis. Currently, ramucirumab is the only therapy specifically tested in patients with α-fetoprotein levels ≥ 400 ng/mL, which is associated with an aggressive disease and poor prognosis. Therefore, ramucirumab is an important treatment option for patients with HCC and α-fetoprotein levels ≥ 400 ng/mL who have been treated with sorafenib.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; alpha-Fetoproteins; Ramucirumab
PubMed: 32034692
DOI: 10.1007/s40265-020-01263-6 -
Liver International : Official Journal... Dec 2019Hepatocellular 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... (Review)
Review
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.
Topics: Antigens, Neoplasm; Biomarkers; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; alpha-Fetoproteins
PubMed: 31436873
DOI: 10.1111/liv.14223 -
Biosensors May 2024Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and... (Review)
Review
Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Biosensing Techniques; Early Detection of Cancer; Biomarkers, Tumor
PubMed: 38785709
DOI: 10.3390/bios14050235 -
Clinics in Laboratory Medicine Jun 2016Biochemical prenatal screening was initiated with the use of maternal serum alpha fetoprotein to screen for open neural tube defects. Screening now includes multiple... (Review)
Review
Biochemical prenatal screening was initiated with the use of maternal serum alpha fetoprotein to screen for open neural tube defects. Screening now includes multiple marker and sequential screening protocols involving serum and ultrasound markers to screen for aneuploidy. Recently cell-free DNA screening for aneuploidy has been initiated, but does not screen for neural tube defects. Although ultrasound is highly effective in identifying neural tube defects in high-risk populations, in decentralized health systems maternal serum screening still plays a significant role. Abnormal maternal serum alpha fetoprotein alone or in combination with other markers may indicate adverse pregnancy outcome in the absence of open neural tube defects.
Topics: Biomarkers; Female; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Spinal Dysraphism; alpha-Fetoproteins
PubMed: 27235920
DOI: 10.1016/j.cll.2016.01.004 -
Journal of Cancer Research and Clinical... Oct 2020Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Alpha-fetoprotein (AFP) is considered as a diagnostic and prognostic tumorous... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Alpha-fetoprotein (AFP) is considered as a diagnostic and prognostic tumorous marker for HCC, and up to 70% of HCC patients showed elevated serum levels of AFP. In the past two decades, evidences have shown that AFP not only is a tumorous biomarker for diagnosing HCC, but also plays a very complicated role in regulating proliferation, apoptosis, and autophagy and inhibiting the immune response of cells. Because AFP is significantly elevated during hepatocarcinogenesis, the role of AFP in the development of HCC is a scientific problem worthy of further exploration. In this review, we reviewed the effects of AFP on hepatocyte malignant transformation and the underlying mechanisms involved in the progression of HCC.
Topics: Apoptosis; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Disease Progression; Humans; Liver Neoplasms; alpha-Fetoproteins
PubMed: 32725355
DOI: 10.1007/s00432-020-03331-6 -
Molecular Cancer Oct 2023To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly...
To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) test's sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; DNA Methylation; Biomarkers, Tumor; Cell-Free Nucleic Acids; Ubiquitin-Protein Ligases
PubMed: 37803338
DOI: 10.1186/s12943-023-01872-1 -
Journal of Environmental Pathology,... 2024Alpha-fetoprotein (AFP) belongs to the albuminoid protein family and is considered as the fetal analog of serum albumin. This plasma protein is initially synthesized in... (Review)
Review
Alpha-fetoprotein (AFP) belongs to the albuminoid protein family and is considered as the fetal analog of serum albumin. This plasma protein is initially synthesized in the fetal liver and yolk sac and shows a maximum peak near the end of the first trimester. Later, concentrations begin to decline prenatally and drop precipitously after birth. This protein has three key ligand-binding pockets for interactions with various biomolecules. It contains multiple phosphorylation and acetylation sites for the regulation of physiological and pathophysiological states. High serum AFP titer is an established biomarker for yolk sac, embryonal and hepatocellular carcinoma. The present review critically analyzes the chemical nature, receptors, clinical implications, and therapeutic aspects of AFP, underpinning the development of different types of cancer.
Topics: Humans; alpha-Fetoproteins; Carcinoma, Hepatocellular; Yolk Sac; Fetus; Liver Neoplasms
PubMed: 38505913
DOI: 10.1615/JEnvironPatholToxicolOncol.2023049145 -
Neoplasma Mar 2018Alpha-fetoprotein (AFP) is a well-known tumor marker of hepatic carcinoma and yolk sac tumor. Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare type of... (Review)
Review
Alpha-fetoprotein (AFP) is a well-known tumor marker of hepatic carcinoma and yolk sac tumor. Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare type of gastric cancer with high malignancy and poor prognosis, which make it different from other types of gastric cancer. This rare gastric cancer patient subgroup is likely frequently misdiagnosed which may be related to lack of knowledge of the disease. The purpose of this article is to summarize the mechanism of AFP positive gastric cancer, classification, biological behavior and treatment, in order to assist clinical practitioners to detect AFPGC earlier and treat it better. Previous studies have showed that AFPGC has a complex pathophysiology mechanism. AFPGC is more aggressive and characterized by stronger proliferation, neovascularization, lymphatic invasion and distant metastasis. Furthermore, so far there has been no standard treatment for patients with AFPGC. Nevertheless, our present study summarizes some effective treatments based on previous research outcome. In conclusion, the present study demonstrates that the importance of detecting AFP routinely in serum and tissues in gastric cancer cases, which will greatly improve the diagnosis rate of AFPGC, and in regards to treatment, surgery, chemotherapy, targeted therapy and interventional treatment may have positive impacts on AFPGC treatment outcome. However, further study with a larger sample is required to confirm the reliability and validity of these methods.
Topics: Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neovascularization, Pathologic; Prognosis; Stomach Neoplasms; alpha-Fetoproteins
PubMed: 29788728
DOI: 10.4149/neo_2018_170207N84 -
Cancer Letters Feb 2015AFP-producing (hepatoid differentiation) gastric cancer (GC) initially reported in 1970 plays an important role in the field of gastrology, which should be distinguished... (Review)
Review
AFP-producing (hepatoid differentiation) gastric cancer (GC) initially reported in 1970 plays an important role in the field of gastrology, which should be distinguished from other solid-type GCs owing to their different biological behavior. This review article aims to summarize the literature related to the role of AFP in gastric cancer and to unveil the underlying mechanism by which AFP-production impacts prognosis of GC patients. The prima facie evidence demonstrated that AFP-producing GC is more aggressive and characterized by a high incidence of venous invasion, lymphatic invasion, and metachronous and synchronous liver metastasis compared with AFP-non producing GC. Furthermore, distant metastasis was frequently observed, leading to a poorer overall prognosis. The underlying molecular mechanism is still obscure and optimal regimen remains undefined well. Nevertheless, our present study advances the knowledge of AFP-producing GC in the field of gastrology. AFP-positivity should be highlighted and an a priori enhancive intervention is needed to improve prognosis in future clinical practice. Personalized medication is strongly suggested.
Topics: Humans; Neoplasm Metastasis; Prognosis; Stomach Neoplasms; alpha-Fetoproteins
PubMed: 25462859
DOI: 10.1016/j.canlet.2014.11.018