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Journal of Cancer Research and... Sep 2018To explore the biological roles of alpha-fetoprotein (AFP), a tumor-associated antigen in human hepatocellular carcinoma (HCC).
AIMS
To explore the biological roles of alpha-fetoprotein (AFP), a tumor-associated antigen in human hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
After knockdown of AFP in HepG2 cells by transfection of specific Stealth™ RNAi, the expression of AFP were detected by reverse transcription polymerase chain reaction at mRNA level and by enzyme-linked immunosorbent assay at the protein level. Then, the effect of silenced AFP on cell proliferation was assessed by dimethylthiazolyl-2,5-diphenyl-tetrazolium bromide assay, and apoptosis assessment with Hoechst33258 and flow cytometry (double stain with fluorescein isothiocyanate/propidium iodide), the roles of AFP in the cell cycle regulation were assessed by flow cytometry. We also detected the expression of some key proteins related to apoptosis pathway by Western immunoblot analysis.
RESULTS
After the transfection for 48 h, the expression of AFP gene was almost abolished, the cell proliferation was inhibited by 47.61%, the number of cells undergoing early apoptosis was significantly increased to 59.47%; cell cycle was arrested with the increase of G0/G1 phase cells from 45.3% to 58.4%. Inhibition of AFP expression also results in decreasing of transforming growth factor-β (TGF-β), mutant P53 expression, and increasing of Bax/Bcl-2 ratio, activation of caspase-3.
CONCLUSIONS
The results suggest that AFP may positively regulate cell proliferation by enhancing the apoptosis resistance via effect on TGF-β and p53/Bax/caspase-3 signaling pathway in HepG2 cells. As such, the knockdown of AFP gene should be further investigated in vivo as a novel approach to HCC treatment.
Topics: Carcinoma, Hepatocellular; Caspase 3; Cell Proliferation; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Hep G2 Cells; Humans; Liver Neoplasms; Signal Transduction; Transforming Growth Factor beta; Tumor Suppressor Protein p53; alpha-Fetoproteins; bcl-2-Associated X Protein
PubMed: 30249880
DOI: 10.4103/0973-1482.180681 -
Fertility and Sterility Aug 2021To determine if high alpha-fetoprotein (AFP) level in vaginal blood collected on a sanitary pad can assist with detecting an active miscarriage.
OBJECTIVE
To determine if high alpha-fetoprotein (AFP) level in vaginal blood collected on a sanitary pad can assist with detecting an active miscarriage.
DESIGN
A prospective cohort study.
SETTING
Academic medical center.
PATIENT(S)
Five groups were evaluated: women with active miscarriage, pregnancy of unknown location, completed miscarriage or extrauterine pregnancy (EUP), ongoing pregnancy, and undergoing elective dilation and curettage (D&C).
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
For each patient, AFP level in the vaginal blood collected on a sanitary pad was quantified.
RESULT(S)
The vaginal blood AFP median levels (and their ranges) were 3.7 IU/mL (0.5-739.2) and 4,542 IU/mL (15.6-100,000) in the active miscarriage (n = 16) and the elective D&C (n = 24) groups, respectively. Alpha-fetoprotein was detected in all elective D&C and active miscarriage cases except in 1 case. In the ongoing pregnancy group (n = 35), only 2 of 35 specimens showed detectable AFP levels. In the pregnancy of unknown location (n = 12) and the completed miscarriage or EUP (n = 10) groups, no AFP was detected. Receiver operating characteristic analysis demonstrated 93.7% sensitivity and 97.8% specificity for the detection of an active miscarriage (cutoff 0.61 IU/mL; area under the curve 0.96).
CONCLUSION(S)
Alpha-fetoprotein can be extracted from vaginal blood collected on sanitary pads. A high level of vaginal AFP can assist with the same-day detection of an active miscarriage. This novel test is useful in differentiating active miscarriages from ongoing pregnancies, completed miscarriages, and EUPs and, therefore, it reduces uncertainty, anxiety level, and number of repeat office visits.
Topics: Abortion, Spontaneous; Adult; Female; Humans; Middle Aged; Pregnancy; Pregnancy Trimester, First; Vagina; Young Adult; alpha-Fetoproteins
PubMed: 33461753
DOI: 10.1016/j.fertnstert.2020.10.006 -
PLoS Neglected Tropical Diseases Jan 2024Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and...
BACKGROUND
Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.
METHODS
A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.
RESULTS
Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.
CONCLUSION
HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.
AUTHOR SUMMARY
Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.
Topics: Animals; Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Epithelial Cell Adhesion Molecule; Clonorchiasis; alpha-Fetoproteins; CA-19-9 Antigen; Neoplasm Staging; China; Prognosis; Clonorchis sinensis; Cholangiocarcinoma; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Liver Cirrhosis; Retrospective Studies
PubMed: 38285640
DOI: 10.1371/journal.pntd.0011906 -
Cancer Medicine Nov 2019The use of alpha-fetoprotein (AFP) testing for the surveillance, diagnosis, and prognosis of hepatocellular carcinoma (HCC) remains controversial. Here, we compared AFP...
BACKGROUND
The use of alpha-fetoprotein (AFP) testing for the surveillance, diagnosis, and prognosis of hepatocellular carcinoma (HCC) remains controversial. Here, we compared AFP testing rates, elevated AFP rates, factors associated with elevated AFP levels, and prognostic factors associated with overall survival (OS) in HCC patients from different ethnic groups.
METHODS
Patients with HCC were identified from the Surveillance, Epidemiology, and End Results registries. Race was categorized as white, black, and others. AFP testing rates and elevated AFP rates were analyzed. Multivariable logistic regression and Cox regression analyses were used to identify independent factors associated with elevated AFP levels and prognosis, respectively. All statistical tests were two sided.
RESULTS
A proportion of 79.2% of total HCC patients had AFP testing reports; 77.3% of white, 79.7% of black, and 81.2% of other races underwent AFP testing. Compared with white and other races, black HCC patients had a higher rate of elevated AFP levels among all patients and the early-stage HCC patient cohort. Elevated AFP level was a significant prognostic factor for all HCC patients in different race groups. Factors associated with elevated AFP level and prognostic factors associated with OS varied significantly by race.
CONCLUSIONS
AFP testing, elevated AFP rates, predictors of elevated AFP level, and prognostic factors associated with OS differed significantly according to race after adjusting for AFP levels among the three groups. AFP testing for the surveillance, diagnosis, and prognosis of HCC patients is strongly recommended, although racial disparities need to be considered.
Topics: Adult; Aged; Carcinoma, Hepatocellular; Early Detection of Cancer; Female; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Logistic Models; Male; Middle Aged; Prognosis; SEER Program; Survival Rate; United States; Up-Regulation; Young Adult; alpha-Fetoproteins
PubMed: 31517445
DOI: 10.1002/cam4.2549 -
BMC Cancer Mar 2019Although men carry a higher risk of hepatocellular carcinoma (HCC) than women, it is still controversial whether men also have a poorer postoperative prognosis. A...
BACKGROUND
Although men carry a higher risk of hepatocellular carcinoma (HCC) than women, it is still controversial whether men also have a poorer postoperative prognosis. A retrospective study was conducted to evaluate the postoperative prognostic predictors of HCC focusing on sex differences.
METHODS
We enrolled 516 consecutive adult patients with HCC (118 women, 398 men), who received surgical resection between January 2000 and December 2007, and were followed-up for >10 years. Clinical and laboratory data together with postoperative outcomes were reviewed.
RESULTS
At baseline, female patients had a higher anti-hepatitis C virus antibody prevalence (P = 0.002); lower hepatitis B virus surface antigen prevalence (P = 0.006); less microvascular invasion (P = 0.019); and lower alpha-fetoprotein (P = 0.023), bilirubin (P = 0.002), and alanine transaminase (P = 0.001) levels. Overall, there were no significant sex differences in terms of intrahepatic recurrence-free survival (RFS), distant metastasis-free survival (MFS), and overall survival (OS). However, subgroup analysis showed that women had favorable RFS (P = 0.019) and MFS (P = 0.034) in patients with alpha-fetoprotein ≤ 35 ng/mL, independent of other clinical variables (adjusted P = 0.008 and 0.043, respectively). Additionally, men had favorable OS in patients with prothrombin time (international normalized ratio [INR]) <1.1 (P = 0.033), independent of other clinical variables (adjusted P = 0.042).
CONCLUSIONS
Female sex is independently associated with favorable postoperative RFS and MFS in patients with alpha-fetoprotein ≤35 ng/mL, while male sex is independently associated with favorable OS in patients with prothrombin time INR <1.1.
Topics: Adult; Aged; Carcinoma, Hepatocellular; Disease-Free Survival; Female; Follow-Up Studies; Health Status Disparities; Hepatectomy; Humans; International Normalized Ratio; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Prognosis; Prothrombin Time; Retrospective Studies; Sex Factors; alpha-Fetoproteins
PubMed: 30894157
DOI: 10.1186/s12885-019-5453-3 -
Journal of Cancer Research and... Apr 2022The number of circulating tumor cells (CTCs) and the presence of circulating tumor microemboli (CTM) were determined in the peripheral blood of patients with liver...
OBJECTIVE AND AIMS
The number of circulating tumor cells (CTCs) and the presence of circulating tumor microemboli (CTM) were determined in the peripheral blood of patients with liver cancer (LC). The relationship between CTCs, CTM, clinicopathologic features, and prognosis of LC was analyzed. The objective of this study was to determine the diagnostic and prognostic value of CTCs/CTM in LC.
SUBJECTS AND METHODS
Patients with LC were enrolled between May 2013 and August 2017, and 67 patients were included in the study. Overall survival curves were built using the Kaplan-Meier method and the log-rank test to identify risk factors. The results were analyzed using a Cox proportional hazards model and expressed as hazard ratio and 95% confidence interval (95% CI).
RESULTS
CTCs and either CTCs or CTM were detected in 27 patients (40.3%) and 29 patients (43.3%). CTM were found in four patients. One-year, 3-year, and 5-year survival rates were 42%, 20%, and 15%, respectively. Univariate Cox regression analysis showed that alpha-fetoprotein (AFP), number of CTCs, presence of CTM, and positive CTC/CTM were associated with survival time. Multivariate Cox regression analysis showed that alpha fetoprotein (AFP), number of CTCs, and presence of CTM were independent risk factors for survival in patients with LC.
CONCLUSION
There was no significant correlation between the number of CTCs, the presence of CTM, and clinicopathologic factors. AFP, number of CTCs, and presence of CTM were independent risk factors for survival in patients with LC.
Topics: Biomarkers, Tumor; Humans; Liver Neoplasms; Neoplastic Cells, Circulating; Prognosis; alpha-Fetoproteins
PubMed: 35645114
DOI: 10.4103/jcrt.jcrt_2311_21 -
Tremor and Other Hyperkinetic Movements... 2019Ataxias represent a challenging group of disorders due to significant clinical overlap. Here, we present a patient with early-onset progressive ataxia, polyneuropathy... (Review)
Review
BACKGROUND
Ataxias represent a challenging group of disorders due to significant clinical overlap. Here, we present a patient with early-onset progressive ataxia, polyneuropathy and discuss how elevation of alpha fetoprotein (AFP) narrows the differential diagnosis.
CASE REPORT
Ataxia, polyneuropathy, and mild elevation of AFP are features compatible with ataxia with oculomotor apraxia type 2 (AOA2) but also with ataxia with oculomotor apraxia type 4 (AOA4). A genetic analysis demonstrated biallelic mutations in senataxin (), confirming the diagnosis of AOA2.
DISCUSSION
Mild elevation of AFP is found in patients with AOA2 and AOA4, and higher levels are commonly seen in ataxia-telangiectasia. AFP is a useful diagnostic tool but not a biomarker for disease progression in AOA2.
Topics: Adult; Biomarkers; Cerebellar Ataxia; Disease Progression; Female; Humans; alpha-Fetoproteins
PubMed: 31656689
DOI: 10.7916/tohm.v0.708 -
Journal of Gastrointestinal and Liver... Jun 2021
Topics: Humans; alpha-Fetoproteins
PubMed: 34174061
DOI: 10.15403/jgld-3440 -
BMC Gastroenterology Apr 2022Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with... (Comparative Study)
Comparative Study
BACKGROUND
Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease.
METHODS
This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods.
RESULTS
Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR).
CONCLUSIONS
The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.
Topics: Bilirubin; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Protein Precursors; Prothrombin; ROC Curve; alpha-Fetoproteins; gamma-Glutamyltransferase
PubMed: 35461226
DOI: 10.1186/s12876-022-02279-w -
Journal of Experimental & Clinical... Apr 2021Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism...
BACKGROUND
Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear.
METHODS
The expression of transcription factor HBP1 and AFP and clinical significance were further analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, Luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1 mice.
RESULTS
The relative expressions of HBP1 and AFP correlated with survival and prognosis in hepatoma patients. HBP1 repressed the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promoted malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibited malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuated AFP effect on PTEN, MMP9 and caspase-3, thus inhibited proliferation and migration, and induced apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributed to hepatoma progression in mice.
CONCLUSIONS
Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the diagnosis and treatment of hepatoma.
Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; High Mobility Group Proteins; Humans; Mice; Repressor Proteins; Signal Transduction; Transfection; alpha-Fetoproteins
PubMed: 33794968
DOI: 10.1186/s13046-021-01881-2