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Journal of Clinical Medicine Jan 2024The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein... (Review)
Review
The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. This article provides a review of the current literature on congenital defects and genetic diseases in the fetus where an elevated level of MS-AFP may serve as the initial diagnostic clue for their detection.
PubMed: 38256600
DOI: 10.3390/jcm13020466 -
Scientific Reports Feb 2024Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the... (Review)
Review
Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.
Topics: Humans; alpha-Fetoproteins; Stomach Neoplasms; Immunohistochemistry; Prognosis; Liver Neoplasms
PubMed: 38355790
DOI: 10.1038/s41598-024-54394-1 -
Clinical and Experimental Medicine Dec 2023We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen...
We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1 mAb and assessed its selectivity. We then evaluated the hLRH1 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1-high, and the remaining 112 cases (65.1%) exhibited hLRH1-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1-high and hLRH1-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1 mAb could provide a powerful tool to validate the relevance of hLRH1 in pathological processes such as tumor development and progression.
Topics: alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; Liver Neoplasms; Phosphorylation; Prognosis; Serine; Humans
PubMed: 37285077
DOI: 10.1007/s10238-023-01098-x -
Journal of Experimental & Clinical... Oct 2023Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of...
BACKGROUND
Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of splicing factor 3b subunit 4 (SF3B4) as a novel non-invasive biomarker for HCC and determine the association between SF3B4 expression and immune cell infiltration.
METHODS
An enzyme-linked immunosorbent assay (ELISA) was used to detect SF3B4 levels in plasma samples obtained from healthy controls (HCs) and patients with chronic hepatitis, liver cirrhosis, and HCC. The expression levels of autoantibodies that detect SF3B4 in the plasma samples of each group of patients were measured. Small extracellular vesicles (EVs) were isolated from patient sera, and the expression levels of EV-SF3B4 were measured using quantitative reverse transcription PCR.
RESULTS
ELISA results confirmed that the expression levels of SF3B4 proteins and autoantibodies in the plasma of patients with HCC were higher than those in HCs. However, their diagnostic performance was not better than that of alpha-fetoprotein (AFP). The mRNA expression of SF3B4 in serum EV increased but not in the buffy coat or serum of patients with HCC. Serum EV-SF3B4 displayed better diagnostic power than AFP for all stages of HCC (AUC = 0.968 vs. 0.816), including early-stage HCC (AUC = 0.960 vs. 0.842), and this was consistent in the external cohort. Single-cell RNA sequencing indicated that SF3B4 expression was correlated with myeloid-derived suppressor cells. The Tumor Immune Estimation Resource database reconfirmed the correlation between SF3B4 expression and immune cell infiltration in HCC.
CONCLUSIONS
SF3B4 may be associated with tumor immune infiltration in HCC, and EV-SF3B4 shows potential as a novel non-invasive diagnostic biomarker of HCC.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Biomarkers, Tumor; RNA Splicing Factors; Extracellular Vesicles; Autoantibodies
PubMed: 37899451
DOI: 10.1186/s13046-023-02867-y -
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 -
Hepatology Forum 2024Alpha-fetoprotein (AFP), an oncofetal protein and biomarker in hepatocellular carcinoma (HCC), has unclear roles and actions.To evaluate the relationships between AFP,...
BACKGROUND AND AIM
Alpha-fetoprotein (AFP), an oncofetal protein and biomarker in hepatocellular carcinoma (HCC), has unclear roles and actions.To evaluate the relationships between AFP, liver function tests, and HCC aggressiveness.
MATERIALS AND METHODS
A retrospective analysis of an HCC patient database was conducted to examine the relationships between baseline serum AFP values, liver function tests, and tumor characteristics.
RESULTS
Statistically significant positive trends were observed between AFP levels and both AST and bilirubin, along with negative trends between AFP and albumin. Significant correlations were also found between AFP and MTD, multifocality, and PVT. Increases in MTD, multifocality, and PVT were noted even at low AFP levels, indicating both AFP-independent and AFP-dependent processes. However, these parameter changes were minimal compared to the substantial changes in AFP levels. Relationships between AFP-related liver and tumor characteristics were found to be similar but inverse to those for albumin, with normal albumin levels associated with more favorable tumor characteristics. Additionally, serum levels of albumin and AFP were inversely related.
CONCLUSION
AFP and albumin levels significantly, but inversely, correlate with tumor parameters, suggesting that albumin may suppress HCC functions and could serve as a potential prognostic marker.
PubMed: 38283277
DOI: 10.14744/hf.2023.2023.0023 -
Epigenetics Dec 2024Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA...
Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Biomarkers, Tumor; DNA Methylation; GTP-Binding Protein beta Subunits
PubMed: 38154055
DOI: 10.1080/15592294.2023.2299044 -
Frontiers in Endocrinology 2024Alpha-fetoprotein (AFP) is a serum protein highly produced during the fetal period. It is also known as a biomarker of various pathologies. Commonly, tumors requiring... (Review)
Review
Alpha-fetoprotein (AFP) is a serum protein highly produced during the fetal period. It is also known as a biomarker of various pathologies. Commonly, tumors requiring diagnosis and monitoring through AFP determination appear during the first year of life, with poorer outcomes when presenting in fetal life. Due to advancements in imaging technology, the detectability of ovarian masses in infants is higher. However, the use of AFP as a biomarker could improve diagnosis in cases when imaging and histological examinations are not sensitive enough to detect tumors. From the outcome of our investigation, it is possible to conclude that there is evidence of an association between increased AFP levels and ovarian masses. However, previous studies have presented contradictory and unverified results, with the authors emphasizing that future research is needed. In this article, an analysis of the available literature on AFP as a biomarker of ovarian masses in children was performed. Two types of literature were reviewed: guidance and published studies (clinical trials, reviews, and systematic reviews). We searched the Embase, PubMed, ScienceDirect, and Web of Science databases to collect essential data.
Topics: Child; Infant; Female; Humans; alpha-Fetoproteins; Biomarkers; Neoplasms, Germ Cell and Embryonal; Fetus; Ovarian Neoplasms
PubMed: 38379864
DOI: 10.3389/fendo.2024.1307619 -
European Journal of Surgical Oncology :... Oct 2023American Joint Committee on Cancer (AJCC)-TNM system doesn't accurately predict prognosis. Our study was designed to identify prognostic factors in patients with...
BACKGROUND
American Joint Committee on Cancer (AJCC)-TNM system doesn't accurately predict prognosis. Our study was designed to identify prognostic factors in patients with multiple hepatocellular carcinoma (MHCC), establish and validate a nomogram model to predict the risk and overall survival (OS) of MHCC patients.
METHODS
We selected eligible HCC patients from the Surveillance, Epidemiology, and End Results (SEER) database, used univariate and multivariate COX regression to determine prognostic factors in MHCC patients, and used these factors to build a nomogram. The accuracy of the prediction was evaluated using the C-index, receiver operating characteristic (ROC) and calibration curve. Decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to compare the nomogram with AJCC-TNM staging system. Finally, the prognosis of different risks was analyzed using Kaplan-Meier (K-M) method.
RESULTS
4950 eligible patients with MHCC were enrolled in our study and randomly assigned to the training cohort and test cohort in a 7:3 ratio. After COX regression analysis, age, sex, histological grade, AJCC-TNM stage, tumor size, alpha-fetoprotein (AFP), surgery, radiotherapy and chemotherapy in total 9 factors could be used to independently determine OS of patients. the above factors were used to construct a nomogram, and the consistency C-index was 0.775. C-index, DCA, NRI and IDI showed that our nomogram was superior to the AJCC-TNM staging system. K-M plots for OS were performed using the log-rank test, the P-value of which was <0.001.
CONCLUSIONS
The practical nomogram can provide more accurate prognostic prediction for multiple hepatocellular carcinoma patients.
Topics: Humans; Nomograms; Carcinoma, Hepatocellular; Liver Neoplasms; Calibration; Databases, Factual; Prognosis
PubMed: 37365056
DOI: 10.1016/j.ejso.2023.06.018 -
International Journal of Surgery Case... Sep 2023Encephalocele is defined as the externalization of brain tissue and/or meninges from the skull through a congenital bony defect. It is one of the most severe neural tube...
INTRODUCTION
Encephalocele is defined as the externalization of brain tissue and/or meninges from the skull through a congenital bony defect. It is one of the most severe neural tube defects.
CASE PRESENTATION
We report a female newborn, weighing 2800 g, APGAR score 8/10. At birth, the clinical examination revealed a weight of 2800 g, a head circumference of 33 cm with a non bulging anterior fontanel.
DISCUSSION
Prenatal diagnosis of encephalocele is made by maternal screening of serum alpha-fetoprotein levels and by ultrasound. On two-dimensional ultrasound, encephalocele appears as a cystic mass with heterogeneous contents in continuity with certain brain structures. 2D ultrasound detects about 80 % of encephaloceles. The diagnosis is easily and confidently made from the ultrasound findings in the second trimester and can also be made in the first trimester. The prognosis of newborns with encephalocele depends on the extent of neural tissue herniation in the sac and the presence of associated anomalies.
CONCLUSION
The purpose of this observation is to highlight the contribution of different antenatal imaging methods in the diagnosis of encephalocele.
PubMed: 37651806
DOI: 10.1016/j.ijscr.2023.108642