Role Of Alpha-fetoprotein Research Articles

AFP-HSP90 mediated MYC/MET activation promotes tumor progression in hepatocellular carcinoma and gastric cancers

Alpha-fetoprotein (AFP) elevation is a well-known biomarker in various diseases, particularly in the diagnosis of hepatocellular carcinoma (HCC). Intracellular AFP has been previously implicated in promoting tumorigenesis. In this study, we discovered that AFP enhances the stability of oncoproteins c-MYC and c-MET, thereby facilitating the progression of liver and gastric tumors. Our findings suggest that AFP acts by stabilizing these oncoproteins, which are clients of heat shock protein 90 (HSP90), and prevents their degradation through ubiquitination. Intriguingly, we identified AFP as a novel co-chaperone of HSP90, demonstrating its ability to regulate the stabilization of HSP90 client proteins. Furthermore, our results indicate that inhibiting AFP or HSP90 enhances the cytotoxicity of chemotherapeutic agents in AFP-producing HCC and gastric cancer cells. These findings have significant implications for the development of therapeutic strategies targeting AFP-producing tumors, as the AFP-HSP90-mediated activation of c-MYC and c-MET provides new insights into potential treatment approaches. In summary, this study sheds light on the role of AFP in promoting tumor progression by stabilizing oncoproteins through its interaction with HSP90. The identification of this mechanism opens up new avenues for therapeutic interventions in AFP-producing tumors.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Role of Alpha-Fetoprotein (AFP) in Diagnosing Childhood Cancers and Genetic-Related Chronic Diseases.

Alpha-fetoprotein (AFP) is a protein commonly found during fetal development, but its role extends beyond birth. Throughout the first year of life, AFP levels can remain high, which can potentially mask various conditions from the neurological, metabolic, hematological, endocrine, and early childhood cancer groups. Although AFP reference values and clinical utility have been established in adults, evaluating AFP levels in children during the diagnostic process, treatment, and post-treatment surveillance is still associated with numerous diagnostic pitfalls. These challenges arise from the presence of physiologically elevated AFP levels, inconsistent data obtained from different laboratory tests, and the limited population of children with oncologic diseases that have been studied. To address these issues, it is essential to establish updated reference ranges for AFP in this specific age group. A population-based study involving a statistically representative group of patients could serve as a valuable solution for this purpose.

Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells.

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.

The Role of Alpha-Fetoprotein (AFP) in Contemporary Oncology: The Path from a Diagnostic Biomarker to an Anticancer Drug.

This article presents contemporary opinion on the role of alpha-fetoprotein in oncologic diagnostics and treatment. This role stretches far beyond the already known one-that of the biomarker of hepatocellular carcinoma. The turn of the 20th and 21st centuries saw a significant increase in knowledge about the fundamental role of AFP in the neoplastic processes, and in the induction of features of malignance and drug resistance of hepatocellular carcinoma. The impact of AFP on the creation of an immunosuppressive environment for the developing tumor was identified, giving rise to attempts at immunotherapy. The paper presents current and prospective therapies using AFP and its derivatives and the gene therapy options. We directed our attention to both the benefits and risks associated with the use of AFP in oncologic therapy.

Role of Alpha Fetoprotein in hepatocellular carcinoma

Hepatocellular carcinoma prevelance rate is higher in Pakistan due to HCV mortality rate, consumption of Alchol, and regular smoking, higher level of AFP progression normal liver cells into fatty liver cells, after inflammation it convert into HCC.In this study, we find the correlation between AFP and hepatocellular carcinoma. AFP involve in development of liver cancer, LFT’s test elevation and HCV also cause of cancer.

Role of Alpha Fetoprotein in Hepatocellular Carcinoma

Role of Alpha Fetoprotein in Hepatocellular Carcinoma

The role of alpha-fetoprotein in the regulation of differentiation and functional activity of myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSC) are innate immune cells that suppress the immune response. MDSC levels increase in pathological conditions as well as during pregnancy. Alpha-fetoprotein (AFP) is synthesized by embryonic tissues and then enters the mother's bloodstream, where it performs both transport and immunomodulatory functions. However, its role in regulating MDSC development has not been studied. In this work, the effect of physiological concentrations of recombinant AFP (10, 50, 100 IU/mL) on the differentiation of human MDSC in the in vitro system was investigated. To work with MDSC, an experimental model was developed to obtain sufficient numbers of these cells by cytokine induction of myeloid cells (CD33+). It was found that AFP at concentrations of 50 and 100 IU/ml increased the total number of MDSC in culture. The detailed analysis subpopulations revealed that the increase was due to monocytic M-MDSC. Thus, for the first time, the direct effect of recombinant AFP on MDSC differentiation have been demonstrated for the first time, which makes it possible in the future to formulate a new concept for its action as a pharmacological drug.

The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has been acknowledged as a leading cause of death among cirrhosis patients. Difficulties in early diagnosis and heterogeneity are obstacles to effective treatment, especially for advanced HCC. Liver transplantation (LT) is considered the best therapy for HCC. Although many biomarkers are being proposed, alpha-fetoprotein (AFP), which was identified over 60 years ago, remains the most utilized. Recently, much hope has been placed in the immunogenicity of AFP to develop novel therapies, such as AFP vaccines and AFP-specific adoptive T-cell transfer (ACT). This review summarizes the performance of AFP as a biomarker for HCC diagnosis and prognosis, as well as its correlation with molecular classes. In addition, the role of AFP in LT is also described. Finally, we highlight the mechanism and application prospects of two immune therapies (AFP vaccine and ACT) for HCC. In general, our review points out the prevalence of AFP in HCC, accompanied by some controversies and novel directions for future research.

Sorafenib and hepatocellular carcinoma: is alpha-fetoprotein a biomarker predictive of tumor biology and primary resistance?

Background: Alpha-fetoprotein (AFP) is the only biomarker with proven prognostic value in advanced hepatocellular carcinoma. Preliminary data indicate crosstalk between AFP and VEGF signaling. Methods: The authors looked at 69 patients with advanced hepatocellular carcinoma who were previously tested for VEGFR2 expression, had available baseline AFP serum concentrations and were treated with sorafenib within clinical trials. Results: Shorter progression-free survival and overall survival were associated with increased AFP level and elevated VEGFR2 staining. At multivariate analysis of AFP level was the only independent prognostic factor for progression-free survival and overall survival. Conclusion:The authors' study confirms the adverse prognostic role of elevated baseline AFP and also suggests a possible role of AFP in primary resistance to sorafenib therapy.

Role of Alpha-Fetoprotein in Hepatocellular Carcinoma Drug Resistance

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Role of alpha-fetoprotein in prognostic evaluation of patients with liver failure

China is a big country with liver diseases, and various hepatitis viruses, drug poisons, and alcohol can cause liver injury and even liver failure. The key to the prognosis of patients with liver failure is liver self-repair and regeneration. Alpha-fetoprotein (AFP) has been extensively studied as a tumor marker in liver cancer, but its role in liver regeneration in patients with liver failure awaits further studies. This article summarizes the basic research on AFP in liver regeneration and the clinical research on AFP in acute liver failure and acute-on-chronic liver failure (ACLF), as well as the previous research findings of our group that AFP is an important prognostic index and regeneration factor for liver regeneration after hepatitis B virus-related ACLF. The analysis shows that further studies on the role of AFP in the prognosis of various types of liver failure and the mechanism of liver regeneration will help deepen our understanding of AFP and liver regeneration, thereby providing new ideas and methods for the clinical diagnosis, treatment, and prognostic evaluation of patients with various types of liver failure.

Role of Alpha-Fetoprotein in Hepatocellular Carcinoma Drug Resistance.

Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and a major cause of cancer-related deaths worldwide because of its high recurrence rate and poor prognosis. Surgical resection is currently the major treatment measure for patients in the early and middle stages of the disease. Because due to late diagnosis, most patients already miss the opportunity for surgery upon disease confirmation, conservative chemotherapy (drug treatment) remains an important method of comprehensive treatment for patients with middle- and late-stage liver cancer. However, multidrug resistance (MDR) in patients with HCC severely reduces the treatment effect and is an important obstacle to chemotherapeutic success. Alpha-fetoprotein (AFP) is an important biomarker for the diagnosis of HCC. The serum expression levels of AFP in many patients with HCC are increased, and a persistently increased AFP level is a risk factor for HCC progression. Many studies have indicated that AFP functions as an immune suppressor, and AFP can promote malignant transformation during HCC development and might be involved in the process of MDR in patients with liver cancer. This review describes drug resistance mechanisms during HCC drug treatment and reviews the relationship between the mechanism of AFP in HCC development and progression and HCC drug resistance.

Effects of alpha-fetoprotein on the occurrence and progression of hepatocellular carcinoma.

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.

Longitudinal assessment of alpha-fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis

Background/aims: Cirrhosis is an important risk factor for hepatocellular carcinoma (HCC), and the surveillance of patients with cirrhosis is, therefore, highly recommended. However, the role of alpha-fetoprotein (AFP) in HCC surveillance is controversial. The aim of this study was to determine the role of AFP in HCC surveillance among patients with cirrhosis.Methods: The study population consisted of 392 patients with cirrhosis. Ultrasound (US) and laboratory tests including AFP were regularly performed to detect HCC development. The cutoff level of AFP for suspicion of HCC was 7 ng/mL.Results: During the median follow-up period of 4.7 (interquartile range, 3.4–5.6) years, HCC developed in 64 (16.3%) patients. Their mean age was 53.6 years, and they were predominantly male (63.5%). For the detection of HCCs, the sensitivity and specificity of US were 56.3% and 100%, respectively. The sensitivity and specificity of AFP were 62.5% and 94.5%, respectively. Using US and AFP in combination increased the sensitivity of surveillance to 89.1% with a specificity of 94.5%. Mean AFP levels were significantly higher in patients with than without HCC at the time of HCC diagnosis, at 6 months and 12 months before the diagnosis. The area under the receiver operating characteristic curve of AFP was highest at the time of HCC diagnosis (0.867), and also was acceptable at 6 months (0.823) and 12 months (0.792) before the diagnosis.Conclusions: These results suggest the complementary use of AFP and US to improve the effectiveness of HCC surveillance in patients with cirrhosis.

1278 Often a Favorable Prognostic Factor: Unusually Elevated Alpha-Fetoprotein (AFP) in a Case of Hepatitis B Virus (HBV) Associated Intrahepatic Cholangiocarcinoma (ICC)

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC), often an incidental finding is a rare tumor of the epithelial cells of the biliary ducts that originate in the liver and extrahepatic bile ducts. Serum alpha-fetoprotein (AFP), as a tumor marker of hepatocellular carcinoma (HCC), and carbohydrate antigen 19-9 (CA 19-9), as a tumor marker of ICC, have been widely used in clinical practice. Although, a subset of patient with ICC (20-25%) present with elevated AFP levels, usually >100 ng/mL and very rarely >1000 ng/mL, its role remains significant in prognosis of ICC. Herein, we discuss a case of Hepatitis B virus (HBV) associated ICC in a young individual with exceptionally high serum AFP levels. CASE DESCRIPTION/METHODS: A 45-year-old male with no apparent past medical history was seen for complaints of fatigue, nausea, anorexia, and associated 34-lb weight loss of 6-weeks duration. Initial labs revealed a chronic HBV infection and an obstructive pattern on liver function tests. Computerized tomography (CT) scan of the abdomen showed a large heterogeneous mass originating from porta hepatis and invading the left lobe of the liver with multiple liver metastases and metastatic lymphadenopathy of the porta hepatis. CT also revealed a mass in the gallbladder along with thrombosed portal vein and intrahepatic biliary dilation (Figures 1 and 2). Magnetic resonance cholangiopancreatography (MRCP) confirmed initial CT findings. Labs revealed an AFP level of 9,715 ng/mL and CA 19-9 level of 554 units/mL. Percutaneous transhepatic cholangiography (PTC) and tissue biopsy revealed liver parenchymal poorly differentiated adenocarcinoma. Attempted internalization of a biliary stent by interventional radiology (IR) was unsuccessful. Management options were discussed with the patient and family who opted for a palliative approach without chemotherapy. DISCUSSION: Intrahepatic cholangiocarcinoma (ICC) is a rare tumor of the epithelial cells of the biliary ducts originating in the liver and extrahepatic bile ducts. ICC tends to be aggressive due to lymph node involvement at diagnosis with intrahepatic, and peritoneal dissemination. Several factors have been implicated in the pathogenesis of ICC including hepatitis B and C viral infections. Role of AFP, often a marker of HCC, is a significant one in prognostication of ICC. Elevated AFP levels, especially with HBV-associated ICC carries a favorable prognosis. Unfortunately, in the case of our patient, due to the advanced nature of his condition, his prognosis remained poor.

Changes in alpha-fetoprotein (AFP) and systemic therapy outcomes in advanced hepatocellular carcinoma (HCC): A multicenter retrospective analysis.

346 Background: AFP is elevated in 70% of HCC and is associated with poor prognosis. The role of AFP as a biomarker of response to systemic treatments has not been established, though small, retrospective studies show association between AFP decline and survival on sorafenib. The relationship between AFP changes and response to immune checkpoint inhibitors (CPI) has not been reported. This study examines AFP changes on treatment for association with outcomes on first-line (1L) SOR and any subsequent CPI in a contemporary, multicenter U.S. population. Methods: Design: Multicenter retrospective case series. Key eligibility: Received 1L SOR or SOR-based combination for advanced HCC; ≥ 1 post-treatment AFP value available; enrolled on IRB-approved registry. Objectives: associate AFP changes within 3 months of start of treatment with overall survival (OS) and time on treatment (TOT) on 1L SOR and any subsequent CPI; associate baseline AFP with OS and TOT for SOR and CPI; relate baseline AFP and changes on treatment to clinical covariates. Results: 152 patients were identified from two centers. Baseline characteristics: M/F 132/20; HBV/HCV/nonviral 40/71/41; Child Pugh A/B 128/23; BCLC A/B/C: 4/15/133. Baseline AFP < 20/ ≥ 400: 43/59. 43 received CPI after SOR. See Table. Baseline AFP was not related to TOT or OS for SOR or CPI. Multivariable analyses for AFP with clinical covariates will be presented. Conclusions: This series is the largest multicenter analysis of AFP response to systemic therapy with SOR and CPI. AFP decrease and increase within the first 3 months of treatment with SOR and CPI were inversely and significantly associated with median OS. AFP warrants further study in randomized cohorts as a biomarker of response to systemic therapy in HCC, now with multiple treatment options available at progression.[Table: see text]

The role of alpha-fetoprotein in regulation of the cytokine profile of activated T-helpers and their conversion in Th17 phenotype

We studied the effect of the native (non-recombinant) alpha-fetoprotein (AFP) on differentiation, proliferation, and cytokine profile of activated helper T cells 17 (Th17). The object of the study was a culture of isolated by immunomagnetic separation helper T cells (CD4+), induced into the Th17 phenotype by using TCR-activator and proinflammatory cytokines (IL-1β and IL-6). AFP had not significant effect on the frequency of Th17 cells (ROR-γτ+) in the helper T cell culture, and did not affect proliferation of these cells, as measured by Ki-67 expression. Evaluation of the cytokine profile of culture supernatants by using the Luminex xMAP technology, revealed that AFP did not affect the levels of IL-4, IL-5, IL-7, IL-8, IL-10, IL-17, IFN-γ and TNF-α, but at concentrations of 50 IU/ml and 100 IU/ml it increased IL-2 production by activated helper T cells. At the same time, AFP suppressed the synthesis of G-CSF and GM-CSF (10 IU/ml), but stimulated the production of CCL4/MIP-1β (100 IU/ml) and CCL2/MCP-1 chemokines (10 IU/ml and 50 IU/ml).

Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling

Alpha-fetoprotein (AFP) has been recognized as a key regulator of cell proliferation in hepatocellular carcinoma (HCC). However, whether AFP functions in cancer cell autophagy remains unknown. This study investigated the effects of AFP on autophagy in HCC cells. The role of AFP was studied in two HCC cell lines, PLC/PRF/5 and HLE. Cell autophagy, apoptosis, proliferation, migration and invasion were analysed with Western blotting, co-immunoprecipitation (CoIP), immunofluorescence, animal models, MTT assays, flow cytometry (FCM), Cell Counting Kit (CCK)-8, and scratch and transwell assays. In PLC/PRF/5 cells, AFP interacted with PTEN and activated PI3K/Akt/mTOR signalling. In HLE cells, overexpressed AFP similarly interacted with PTEN, leading to PI3K/Akt/mTOR activation and reduced cell autophagy. When AFP was silenced in PLC/PRF/5 cells, cell proliferation, tumour growth, migration and invasion were inhibited, and the numbers of S-phase and apoptotic cells were increased. In contrast, AFP overexpression in HLE cells enhanced cell proliferation, migration and invasion and reduced apoptosis. AFP-dependent autophagy, proliferation, migration and apoptosis were inhibited by rapamycin. In summary, AFP plays critical roles in the inhibition of autophagy and apoptosis in HCC cells and promotes proliferation, migration and invasion. The role of AFP in autophagy inhibition in HCC cells may involve the activation of PI3K/Akt/mTOR signalling.

Assessment of Alpha-1-Acid Glycoprotein as a new Biomarker for Hepatocellular Carcinoma

Background and study aim: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We aimed to evaluate the performances of serum alpha -1-acid glycoprotein (AAG) for the diagnosis of HCC, especially for HCC with low alpha-fetoprotein (AFP). Patients and Methods: Ninety patients included in this study, Session [CurrentTestPartID] had HCC, and 30 (50%) of these were AFP low HCC (AFP ≤20 ng/mL). The remaining 30 patients were chronic hepatitis C and cirrhosis without HCC as control group. Plasma AAG was analyzed using quantitative enzyme immunoassay technique. Results: Serum level of AAG was significantly elevated in low AFP HCC group compared with high AFP HCC and cirrhotic without HCC group, 1307.20 ± 9627 vs (850.82 ± 795.14 and 309.77± 220.17 respectively). Receiver operating characteristic (ROC) curve showed that the best cut off for AAG and AFP was 740 μg/ml and 20 ng/mL respectively. The area under the curve of AAG was significantly higher than that for AFP (0.95 vs 0.92) respectively. AAG at a cut-off value of 740 μg/ml provides higher sensitivity (73.3% vs 62%, respectively) and specificity (74.0%, and 71%, respectively) in low AFP HCC than high AFP HCC Conclusion: The role of AFP in the diagnosis of HCC is limited; AAG had better performance in diagnosing HCC patients with low AFP. So Serum level of AAG might be used as a potential diagnostic marker for hepatocellular carcinoma.