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World Journal of Gastroenterology Jan 2016Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria,... (Review)
Review
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor's biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as (18)F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Fluorodeoxyglucose F18; Humans; Liver Neoplasms; Liver Transplantation; Patient Selection; Positron-Emission Tomography; Prognosis; Protein Precursors; Prothrombin; RNA, Messenger; alpha-Fetoproteins
PubMed: 26755873
DOI: 10.3748/wjg.v22.i1.232 -
Scientific Reports Aug 2022To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in...
To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15-20 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer-lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best.
Topics: Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Female; Humans; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Trisomy; Trisomy 18 Syndrome; alpha-Fetoproteins
PubMed: 35948592
DOI: 10.1038/s41598-022-16807-x -
Bioengineered Dec 2021ABSTRCTThe α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) have certain diagnostic value, but their potential value in prognosis prediction,... (Clinical Trial)
Clinical Trial
Potentiality of α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) in prognosis prediction and immunotherapy response for patients with hepatocellular carcinoma.
ABSTRCTThe α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) have certain diagnostic value, but their potential value in prognosis prediction, especially immunotherapy response prediction, remains unclear in liver cancer. Through the tumor-free survival (TFS) and overall survival (OS) rates analyses of serum AFP and sICAM-1 levels in 87 patients with primary hepatocellular carcinoma (HCC), the patients whose AFP and sICAM-1 levels were normal (AFP < 20 μg/L or sICAM-1 < 1000 μg/L) before surgery or recovered to normal after surgery exhibited a lower tumor recurrence rate and better OS than patients with elevated serum levels of the two markers. Combined analysis showed that patients with synchronously elevated levels of AFP and sICAM-1 showed the lowest TFS and OS. In addition, the RNA-seq data and clinical information of The Cancer Genome Atlas Liver Hepatocellular Carcinoma were collected to analyze the predictive values of AFP and ICAM-1 in the diagnosis, prognosis and immunotherapy of HCC. The results indicated that the combined application of the two indicators had higher accuracy in both the diagnosis and prognostic prediction of HCC by receiver operating characteristic curves. AFP and ICAM-1 were significantly correlated with multiple immune cells in HCC samples but not in normal samples. The patients with low expression of the two indicators were most likely to benefit from the immune checkpoint blockade therapy. In conclusion, AFP and ICAM-1 play vital roles in the diagnosis, prognostic prediction, and immunotherapy of HCC, suggesting that they are considered as prognostic predictors in clinical practice.
Topics: Adult; Aged; Carcinoma, Hepatocellular; Disease-Free Survival; Female; Humans; Immunotherapy; Intercellular Adhesion Molecule-1; Liver Neoplasms; Male; Middle Aged; Neoplasm Proteins; Survival Rate; alpha-Fetoproteins
PubMed: 34696675
DOI: 10.1080/21655979.2021.1990195 -
Ginekologia Polska 2022Alpha-fetoprotein (AFP) is a serum protein, which is characteristic of the fetal development period and a well-known oncological marker. The predominance of AFP among...
Alpha-fetoprotein (AFP) is a serum protein, which is characteristic of the fetal development period and a well-known oncological marker. The predominance of AFP among serum proteins is common in fetal life, whereas after birthing its functions are gradually taken over by albumins. An understanding of the mechanism of AFP transfer between fetus and mother has led to the development of screening tests for identifying neural tube defects and Down's syndrome. Currently, the knowledge on patophysiology and the possible importance of AFP in perinatology and fetal medicine extends far beyond those 2 disease states. Throughout the 50 years of research on AFP, there has been dynamic progress of diagnostic techniques, from the qualitative ones that are used solely for scientific studies to the widely used radioimmunoassays and immunoenzymatic assays (enzyme-linked immunosorbent assay, chemiluminescence immunoassay, time-resolved fluorescence immunoassay). Some genetic mutations cause complete inhibition of AFP production by the fetus. This affects the results of screening tests during pregnancy, and also leads to constantly high levels of AFP in adults, which are not linked to oncogenesis.
Topics: Pregnancy; Adult; Female; Humans; Prenatal Diagnosis; Perinatology; alpha-Fetoproteins; Down Syndrome; Fetus
PubMed: 35072257
DOI: 10.5603/GP.a2021.0226 -
The Journal of International Medical... Aug 2022Alpha-fetoprotein(AFP)-producing colorectal cancer is a rare form of colorectal cancer with a high degree of malignancy, advanced stage, strong invasiveness, poor... (Review)
Review
Alpha-fetoprotein(AFP)-producing colorectal cancer is a rare form of colorectal cancer with a high degree of malignancy, advanced stage, strong invasiveness, poor response to treatment, rapid progression, and poor prognosis. Herein, we present the case of a middle-aged (in his 50s) male patient who underwent left neck lymph node biopsy due to "left neck lymph node enlargement for 5 months." Biopsy results revealed metastatic adenocarcinoma, and computed tomography examination of the chest and abdomen suggested a malignant tumor of the sigmoid colon with multiple metastases. Subsequently, the patient underwent colonoscopy, and the pathological result was colonic adenocarcinoma. Regarding tumor markers, serum alpha-fetoprotein (AFP) was 214 ng/mL. The patient received first- and second-line treatments for colon cancer, but progression-free survival was short. AFP was consistently elevated; after 8 months, the patient had AFP levels of 11,371.8 ng/mL, and imaging confirmed disease progression. The patient subsequently died, with an overall survival of more than 9 months. Compared with other tumor markers, AFP better reflects tumor progression in AFP-producing colorectal cancer.
Topics: Adenocarcinoma; Biomarkers, Tumor; Colonic Neoplasms; Colorectal Neoplasms; Humans; Male; Middle Aged; alpha-Fetoproteins
PubMed: 35999811
DOI: 10.1177/03000605221117218 -
Experimental Biology and Medicine... May 2022The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free β-hCG), and open neural tube defects...
The correlation of maternal serum alpha-fetoprotein (AFP) variants (AFP-L2, AFP-L3), free beta-human chorionic gonadotropin (free β-hCG), and open neural tube defects (ONTDs) during the second trimester, and the screening efficiency of different risk models remain indistinct. We conducted a retrospective case-control study, and studied 57 pregnant women with ONTD fetuses and 569 pregnant women with normal fetuses. The receiver operating characteristic curve method indicated the best cutoff value and area under the curve (AUC). The predictive value of ONTD risk models by free β-hCG, AFP, AFP-L2, and AFP-L3 was investigated via integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Compared to the control group, AFP, AFP-L2, and AFP-L3 levels were significantly higher, while free β-hCG level was significantly lower in the study group. The triple-index model of free β-hCG + AFP-L2 + AFP-L3 and the dual-index model of AFP-L2 + AFP-L3 showed the best predictive values, respectively (AUC = 0.905; AUC = 0.885). The order of the single-index model AUCs was AFP-L3 > AFP-L2 > AFP > free β-hCG. The negative predictive value, false positive rate, and negative likelihood ratio of AFP-L2, AFP-L3 alone, or combined with free β- hCG were better than those of AFP alone; however, the positive likelihood ratio was the opposite. The replacement of AFP by AFP-L2 or AFP-L3 combined with free β-hCG increased the IDI and NRI for predicting ONTD. The top five DCAs were AFP-L2 + free β-hCG, free β-hCG, AFP-L3, AFP + free β-hCG, and AFP. Indicators of maternal serum free β-hCG, AFP-L2, and AFP-L3 in the second trimester exhibited high sensitivity and specificity screening for ONTD fetuses. Risk models constructed using AFP-L2 + AFP-L3 and AFP-L2 + AFP-L3 + free β-hCG demonstrated better screening efficiency.
Topics: Biomarkers; Case-Control Studies; Chorionic Gonadotropin, beta Subunit, Human; Female; Fetus; Humans; Neural Tube Defects; Pregnancy; Prenatal Diagnosis; Retrospective Studies; alpha-Fetoproteins
PubMed: 35238224
DOI: 10.1177/15353702221080458 -
BMJ Case Reports Jul 2021Hepatoid adenocarcinoma (HAC) is a rare tumour that produces an alpha-fetoprotein (AFP) mimicking hepatocellular carcinoma (HCC). Adrenal HAC is exceedingly rare. Here...
Hepatoid adenocarcinoma (HAC) is a rare tumour that produces an alpha-fetoprotein (AFP) mimicking hepatocellular carcinoma (HCC). Adrenal HAC is exceedingly rare. Here we report extremely high AFP-producing adrenal HAC, the first case in Thailand. A 47-year-old man presented with left flank pain and weight loss for 2 months. A palpably huge left flank mass was observed on physical examination. CT revealed a 7 cm enhanced mass involving the left adrenal gland and multiple contrast-enhanced hypodense masses in both liver lobes. The largest was a 3.7 cm at liver segment-VII without cirrhotic background, with an AFP level of 321 495 ng/mL. Both adrenal and liver biopsies were performed. This patient received a diagnosis of advanced adrenal HAC. Unfortunately, the tumour progressed, causing massive upper gastrointestinal bleeding and death. Adrenal HAC is challenging to diagnose, which multifocal HCC, pheochromocytoma and adrenocortical carcinoma should be excluded. Surgical resection is preferred among resectable patients. However, no systemic therapy has been standardised.
Topics: Adenocarcinoma; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Male; Middle Aged; Thailand; alpha-Fetoproteins
PubMed: 34253511
DOI: 10.1136/bcr-2020-239830 -
Lipids in Health and Disease Apr 2016Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with...
BACKGROUND
Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population.
METHODS
A cross-sectional study was performed with 7,755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome.
RESULTS
Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides.
CONCLUSIONS
These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; China; Cholesterol, HDL; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Risk Factors; Waist Circumference; Young Adult; alpha-Fetoproteins
PubMed: 27121855
DOI: 10.1186/s12944-016-0256-x -
BMC Medical Genomics Dec 2020Serum alpha-fetoprotein (AFP) is the approved serum marker for hepatocellular carcinoma (HCC) screening. However, not all HCC patients show high (≥ 20 ng/mL) serum...
BACKGROUND
Serum alpha-fetoprotein (AFP) is the approved serum marker for hepatocellular carcinoma (HCC) screening. However, not all HCC patients show high (≥ 20 ng/mL) serum AFP, and the molecular mechanisms of HCCs with normal (< 20 ng/mL) serum AFP remain to be elucidated. Therefore, we aimed to identify biological features of HCCs with normal serum AFP by investigating differential alternative splicing (AS) between HCCs with normal and high serum AFP.
METHODS
We performed a genome-wide survey of AS events in 249 HCCs with normal (n = 131) and high (n = 118) serum AFP levels using RNA-sequencing data obtained from The Cancer Genome Atlas.
RESULTS
In group comparisons of RNA-seq profiles from HCCs with normal and high serum AFP levels, 161 differential AS events (125 genes; ΔPSI > 0.05, FDR < 0.05) were identified to be alternatively spliced between the two groups. Those genes were enriched in cell migration or proliferation terms such as "the cell migration and growth-cone collapse" and "regulation of insulin-like growth factor (IGF) transport and uptake by IGF binding proteins". Most of all, two AS genes (FN1 and FAM20A) directly interact with AFP; these relate to the regulation of IGF transport and post-translational protein phosphorylation. Interestingly, 42 genes and 27 genes were associated with gender and vascular invasion (VI), respectively, but only eighteen genes were significant in survival analysis. We especially highlight that FN1 exhibited increased differential expression of AS events (ΔPSI > 0.05), in which exons 25 and 33 were more frequently skipped in HCCs with normal (low) serum AFP compared to those with high serum AFP. Moreover, these events were gender and VI dependent.
CONCLUSION
We found that AS may influence the regulation of transcriptional differences inherent in the occurrence of HCC maintaining normal rather than elevated serum AFP levels.
Topics: Alternative Splicing; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Survival Rate; alpha-Fetoproteins
PubMed: 33371894
DOI: 10.1186/s12920-020-00836-4 -
Journal of Cellular and Molecular... Nov 2022Alpha fetoprotein (AFP) is associated with hepatocellular carcinoma (HCC) by stimulating the proliferation, metastasis and drug resistance. The application of AFP...
Alpha fetoprotein (AFP) is associated with hepatocellular carcinoma (HCC) by stimulating the proliferation, metastasis and drug resistance. The application of AFP fragments to inhibit the malignant behaviours induced by AFP is a new strategy for the treatment of HCC. In an effort to design, screen and discover drugs, we attempted to express different human AFP fragments (AFP , AFP and AFP ) in a Bac-to-Bac system. We found that the AFP fragment was highly expressed in the system. Then, we assessed the bioactivity of the fragment in the human liver cancer cell line Bel7402, and the results indicated that the AFP fragment synergized with sorafenib to inhibit the hepatoma cell growth and migration and promote the apoptosis. This study provides a method to produce significant AFP fragments to screen AFP inhibitors for use in HCC therapy.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Sorafenib; Cell Line, Tumor; Cell Proliferation; Apoptosis
PubMed: 36181321
DOI: 10.1111/jcmm.17565