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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 -
American Journal of Physiology.... Feb 2020Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to...
Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort ( = 40). The selected proteins were confirmed using ELISA in a validation cohort ( = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson's = 0.944, < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result. This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.
Topics: Adult; Aged; Biomarkers; Carcinoma, Hepatocellular; Cohort Studies; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Mass Screening; Middle Aged; Orosomucoid; Proteome; Reproducibility of Results; alpha-Fetoproteins
PubMed: 31736338
DOI: 10.1152/ajpgi.00267.2019 -
Obstetrics and Gynecology Mar 2023Black racial designation is the only race for which adjustment is recommended for maternal prenatal serum alpha-fetoprotein (AFP) screening. The objective of this study...
OBJECTIVE
Black racial designation is the only race for which adjustment is recommended for maternal prenatal serum alpha-fetoprotein (AFP) screening. The objective of this study is to reevaluate the relationship between maternal race and maternal serum AFP values in prenatal analyte screening.
METHODS
This was a single-center retrospective analysis of patients who underwent prenatal analyte screening between January 2007 and December 2020. Nomograms for raw maternal serum AFP values by gestational age were created and compared between patients identified as "Black" and "non-Black" on the laboratory requisition. Multivariable linear regression models were created to evaluate the relationship among gestational age, maternal weight, and maternal race on maternal serum AFP levels. The new models were compared with the laboratory-derived calculations, which used historically determined race adjustments.
RESULTS
A total of 43,997 patients underwent analyte screening, and 27,710 patients had complete data for analysis. Of these, 6% were identified as Black. Black patients had laboratory blood draws at a mean gestational age of 123 days, compared with 120 days in non-Black patients ( P <.001), and had higher maternal weight (mean 170 vs 161 lbs, P <.001). Nomograms for raw maternal serum AFP values did not differ between Black and non-Black patients ( P =.065). When adjusted for gestational age and maternal weight, no difference in maternal serum AFP values was identified between Black and non-Black individuals ( P =.81).
CONCLUSION
No difference in maternal serum AFP values was identified between Black and non-Black pregnant individuals when adjusted by maternal weight and gestational age at blood draw. These findings suggest that routine race-based adjustment of maternal serum AFP screening should be discontinued.
Topics: Pregnancy; Female; Humans; Infant; alpha-Fetoproteins; Retrospective Studies; Prenatal Diagnosis
PubMed: 36735409
DOI: 10.1097/AOG.0000000000005045 -
Discovery Medicine Jun 2016Human hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Alpha-fetoprotein (AFP) is perhaps the best-defined tumor marker for HCC,... (Review)
Review
Human hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Alpha-fetoprotein (AFP) is perhaps the best-defined tumor marker for HCC, and as such, it is widely used in clinical settings as an adjuvant diagnostic and prognostic tool. Up to 70% of HCC cases exhibit elevated serum level of AFP, but its pathophysiological functions in HCC are poorly defined. It is now known that AFP is not just a fetal form of carrier protein and a tumor marker, it is also critically involved in the regulation of several important cellular functions, such as cell growth, differentiation, apoptosis, angiogenesis, and immune regulation. In this mini-review, we summarize the recent development of AFP in hepatocellular carcinoma.
Topics: Apoptosis; Biomarkers, Tumor; Carcinoma, Hepatocellular; Dendritic Cells; Early Detection of Cancer; Humans; Immune Tolerance; Immunity, Cellular; Immunotherapy, Adoptive; Liver; Liver Neoplasms; Molecular Targeted Therapy; Prognosis; Risk Factors; alpha-Fetoproteins
PubMed: 27448785
DOI: No ID Found -
Discovery Medicine Apr 2023Hepatocellular carcinoma development and many other tumors are closely related to alpha-fetoprotein (AFP), its determination can be used as a positive test for tumors.... (Review)
Review
Hepatocellular carcinoma development and many other tumors are closely related to alpha-fetoprotein (AFP), its determination can be used as a positive test for tumors. It is mainly used clinically as a serum marker to diagnose and monitor the efficacy of primary hepatocellular carcinoma. Therefore, a variety of biosensors have been developed to detect AFP. Electrochemical sensors integrate a variety of detection methods. They have inherent advantages over other types of sensors, they are fast, portable, simple, and highly sensitive. Some meaningful electrochemical biosensors work with nanomaterials acting as signal amplification elements or as signal amplification catalysts. This review introduced the field of biosensors and discuss about the use of nanomaterials in electrochemical sensing, specificity electrochemical biosensing of AFP. The study ends with a discussion about the prospects for nanomaterial-based signal amplification and future research directions.
Topics: Humans; alpha-Fetoproteins; Carcinoma, Hepatocellular; Nanostructures; Biosensing Techniques; Liver Neoplasms
PubMed: 37105920
DOI: 10.24976/Discov.Med.202335175.10 -
Scientific Reports Sep 2022Metastasis is crucial for the prognosis of hepatocellular carcinoma (HCC). Distinguishing the potential risk factors for distant metastasis in small HCC...
Metastasis is crucial for the prognosis of hepatocellular carcinoma (HCC). Distinguishing the potential risk factors for distant metastasis in small HCC (diameter ≤ 5 cm) is of great significance for improving the prognosis. HCC patients in the Surveillance, Epidemiology and End Results (SEER) registry with tumors ≤ 5 cm in diameter between January 2010 and December 2015 were retrieved. Demographic and clinicopathological metrics were extracted, including age, sex, race, marital status, tumor size, histological grade, T stage, N stage, M stage, alpha-fetoprotein (AFP), and liver fibrosis score. Univariate and multivariate logistic regression analyses were used to identify independent risk factors correlated with extrahepatic metastasis in small HCC. Propensity score matching (PSM) analysis was performed to balance the confounding factors in baseline characteristics. A total of 4176 eligible patients were divided into a non-metastasis group (n = 4033) and a metastasis group (n = 143) based on metastasis status. In multivariate analysis, larger tumor size, poor histological differentiation, regional lymph node metastasis, and elevated serum AFP levels were identified as independent risk factors for distant metastasis (P < 0.05), while age, sex, race, marital status, and liver fibrosis score were not associated with extrahepatic metastasis. After propensity score analysis, the AFP level was no longer associated with metastatic risk. The present study provided no evidence for a correlation between the clinical threshold of AFP and metastasis in small hepatocellular carcinoma.
Topics: Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Prognosis; alpha-Fetoproteins
PubMed: 36127436
DOI: 10.1038/s41598-022-19531-8 -
Annals of Surgical Oncology Feb 2024According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, tumor burden and liver function, but not tumor biology, are the key factors in determining tumor staging...
Prognostic Value of Serum α-Fetoprotein Level as an Important Characteristic of Tumor Biology for Patients Undergoing Liver Resection of Early-Stage Hepatocellular Carcinoma (BCLC Stage 0/A): A Large Multicenter Analysis.
BACKGROUND AND OBJECTIVE
According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, tumor burden and liver function, but not tumor biology, are the key factors in determining tumor staging and treatment modality, and evaluating treatment prognosis. The serum α-fetoprotein (AFP) level is an important characteristic of hepatocellular carcinoma (HCC) biology, and we aimed to evaluate its prognostic value for patients undergoing liver resection of early-stage HCC.
METHODS
Patients who underwent curative liver resection for early-stage HCC were identified from a multi-institutional database. Patients were divided into three groups according to preoperative AFP levels: low (< 400 ng/mL), high (400-999 ng/mL), and extremely-high (≥ 1000 ng/mL) AFP groups. Overall survival (OS) and recurrence rates were compared among these three groups.
RESULTS
Among 1284 patients, 720 (56.1%), 262 (20.4%), and 302 (23.5%) patients had preoperative low, high, and extremely-high AFP levels, respectively. The cumulative 5-year OS and recurrence rates were 71.3 and 38.9% among patients in the low AFP group, 66.3 and 48.5% in the high AFP group, and 45.7 and 67.2% in the extremely-high AFP group, respectively (both p < 0.001). Multivariate Cox regression analysis identified both high and extremely-high AFP levels to be independent risk factors of OS (hazard ratio [HR] 1.275 and 1.978, 95% confidence interval [CI] 1.004-1.620 and 1.588-2.464, respectively; p = 0.047 and p < 0.001, respectively) and recurrence (HR 1.290 and 2.050, 95% CI 1.047-1.588 and 1.692-2.484, respectively; p = 0.017 and p < 0.001, respectively).
CONCLUSIONS
This study demonstrated the important prognostic value of preoperative AFP levels among patients undergoing resection for early-stage HCC. Incorporating AFP to prognostic estimation of the BCLC algorithm can help guide individualized risk stratification and identify neoadjuvant/adjuvant treatment necessity.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Liver Neoplasms; alpha-Fetoproteins; Neoplasm Staging; Biology; Retrospective Studies; Neoplasm Recurrence, Local
PubMed: 37925654
DOI: 10.1245/s10434-023-14525-w -
Neoplasma Sep 2021Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress...
Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.
Topics: Apoptosis; Carcinoma, Hepatocellular; Cell Line; Endoplasmic Reticulum Stress; Humans; Liver Neoplasms; alpha-Fetoproteins
PubMed: 34374292
DOI: 10.4149/neo_2021_210205N180 -
Nihon Rinsho. Japanese Journal of... Mar 2015
Topics: Glypicans; Humans; Molecular Targeted Therapy; Neoplasms; alpha-Fetoproteins
PubMed: 25857135
DOI: No ID Found -
Bioscience Reports Feb 2017α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a...
α-fetoprotein (AFP) is an early serum growth factor in foetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a tumour-specific biomarker have concluded that AFP is an important target for cancer treatment. AFP also plays an immunomodulatory role in the treatment of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis and thyroiditis. In an effort to support biochemical screening and drug design and discovery, we attempted to express and purify human AFP in a Bac-to-Bac system. Two key factors affecting the expression of recombinant human AFP (R-AFP), namely the infectious baculovirus inoculum volume and the culturing time post-infection, were optimized to maximize the yield. We achieved a high yield of approximately 1.5 mg/l of harvested medium with a 72-96 h incubation period after infection and an inoculum volume ratio of 1:100. We also assessed the role of R-AFP in the proliferation of the human liver cancer cell line Bel 7402, and the results indicated that R-AFP promoted the growth of hepatoma cells. We concluded that this method can produce high yields of R-AFP, which can be used for studies related to AFP.
Topics: Animals; Baculoviridae; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Culture Media; Drug Design; Drug Evaluation, Preclinical; Humans; Immunologic Factors; Insecta; Recombinant Proteins; alpha-Fetoproteins
PubMed: 27913752
DOI: 10.1042/BSR20160161