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Biosensors Sep 2022Alpha-fetoprotein (AFP) is widely-known as the most commonly used protein biomarker for liver cancer diagnosis at the early stage. Therefore, developing the highly... (Review)
Review
Alpha-fetoprotein (AFP) is widely-known as the most commonly used protein biomarker for liver cancer diagnosis at the early stage. Therefore, developing the highly sensitive and reliable method of AFP detection is of essential demand for practical applications. Herein, two types of aptamer-based AFP detection methods, i.e., optical and electrochemical biosensors, are reviewed in detail. The optical biosensors include Raman spectroscopy, dual-polarization interferometry, resonance light-scattering, fluorescence, and chemiluminescence. The electrochemical biosensors include cyclic voltammetry, electrochemical impedance spectroscopy, and giant magnetic impedance. Looking into the future, methods for AFP detection that are high sensitivity, long-term stability, low cost, and operation convenience will continue to be developed.
Topics: alpha-Fetoproteins; Electrochemical Techniques; Limit of Detection; Biosensing Techniques; Aptamers, Nucleotide
PubMed: 36290918
DOI: 10.3390/bios12100780 -
Single-cell characteristics and malignancy regulation of alpha-fetoprotein-producing gastric cancer.Cancer Medicine May 2023To characterize alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) at the single-cell level and to identify regulatory factors for AFP expression and malignancy.
OBJECTIVE
To characterize alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) at the single-cell level and to identify regulatory factors for AFP expression and malignancy.
METHODS
ScRNA-seq was performed on two tumors collected from patients with AFPGC. InferCNV and sub-clustering were applied to identify typical AFPGC cells, followed by AddModuleScore, pathway enrichment, Pseudo-time, and Scenic analyses. Data from a gastric cancer (GC) cohort were collected for conjoint analysis. The analytical results were verified by cell experiments and immunohistochemistry.
RESULTS
AFPGC cells are similar to hepatocytes in transcriptome and transcriptional regulation, with kinetic malignancy-related pathways, compared to the common malignant epithelium. In addition, compared to common GC cells, malignancy-related pathways, such as epithelial-mesenchymal transition (EMT) and angiogenesis, were upregulated in AFPGC. Mechanistically, Dickkopf-1 (DKK1) was found to be associated with AFP expression and malignant phenotype upon combining our scRNA-seq data with a public database, which was further verified by a series of in vitro experiments and immunohistochemistry.
CONCLUSION
We demonstrated the single-cell characteristics of AFPGC and that DKK1 facilitates AFP expression and malignancy.
Topics: Humans; Stomach Neoplasms; alpha-Fetoproteins; Prognosis
PubMed: 37017469
DOI: 10.1002/cam4.5883 -
Clinical and Experimental Hypertension... Dec 2023To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD).
BACKGROUND
To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD).
METHODS
A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women's Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free β-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups.
RESULTS
The AFP MoM and free β-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (≥35 years), increased free β-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group.
CONCLUSIONS
Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (≥35 years) and hepatitis B carriers also increased maternal serum AFP significantly.
Topics: Pregnancy; Infant; Humans; Female; Male; Adult; alpha-Fetoproteins; Placenta Previa; Retrospective Studies; Placenta; Chorionic Gonadotropin, beta Subunit, Human
PubMed: 36849437
DOI: 10.1080/10641963.2023.2175848 -
Molecular Cancer Oct 2023To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly...
To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) test's sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; DNA Methylation; Biomarkers, Tumor; Cell-Free Nucleic Acids; Ubiquitin-Protein Ligases
PubMed: 37803338
DOI: 10.1186/s12943-023-01872-1 -
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 -
The American Journal of Gastroenterology Dec 2022Abdominal ultrasound, with or without alpha-fetoprotein, is the recommended strategy for hepatocellular carcinoma (HCC) surveillance but misses over one-third of HCC at...
Abdominal ultrasound, with or without alpha-fetoprotein, is the recommended strategy for hepatocellular carcinoma (HCC) surveillance but misses over one-third of HCC at an early stage. Emerging imaging modalities, including computed tomography and magnetic resonance imaging, have early data showing high sensitivity for early-stage HCC, but potential issues such as radiologic capacity, patient acceptance, cost-effectiveness, and need for validation in Western non-hepatitis B virus populations still need to be evaluated. Similarly, blood-based biomarker panels, including GALAD and liquid biopsy techniques, have shown promising data in phase II case-control studies and may concurrently help address issues of surveillance underuse; however, these tools require validation in phase III and IV cohort studies. While awaiting prospective validation data for these emerging strategies, ultrasound with or without alpha-fetoprotein remains the current gold standard HCC surveillance strategy.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Ultrasonography; Magnetic Resonance Imaging; Liver Cirrhosis
PubMed: 36114768
DOI: 10.14309/ajg.0000000000002015 -
Current Oncology (Toronto, Ont.) Oct 2022Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients with advanced chronic liver disease (AdvCLD) and small tumors for the last 25 years. For HCC patients undergoing liver transplantation, alpha fetoprotein (AFP) has increasingly been applied as an independent predictor for overall survival, disease free recurrence, and waitlist drop out. In addition to static AFP, newer studies evaluating the AFP dynamic response to downstaging therapy show enhanced prognostication compared to static AFP alone. While AFP has been utilized to select HCC patients for transplant, despite years of allocation policy changes, the US allocation system continues to take a uniform approach to HCC patients, without discriminating between those with favorable or unfavorable tumor biology. We aim to review the history of liver allocation for HCC in the US, the utility of AFP in liver transplantation, the implications of weaving AFP as a biomarker into policy. Based on this review, we encourage the US transplant community to revisit its HCC organ allocation model, to incorporate more precise oncologic principles for patient selection, and to adopt AFP dynamics to better stratify waitlist dropout risk.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Transplantation; Liver Neoplasms; Neoplasm Recurrence, Local; Biomarkers
PubMed: 36290870
DOI: 10.3390/curroncol29100593 -
Disease Markers 2022This study was conducted to investigate the effect of alpha-fetoprotein (AFP) ratio on the prognosis of AFP-positive hepatocellular carcinoma (HCC) patients after...
BACKGROUND
This study was conducted to investigate the effect of alpha-fetoprotein (AFP) ratio on the prognosis of AFP-positive hepatocellular carcinoma (HCC) patients after hepatectomy.
METHODS
We retrospectively included 879 HCC patients with AFP-positive who underwent hepatectomy from February 2012 to October 2017 and randomly divided into training cohort and validation cohort. AFP ratio was equal to the AFP level within one week before hepatectomy to AFP level within 20-40 days after surgery. The end point of follow-up was disease-free survival (DFS) and overall survival (OS).
RESULTS
AFP ratio was not associated with clinical characteristics in training cohort and validation cohort. According to the X-tile software, the optimum cut-off point was 17.8 for AFP ratio. Significant differences between AFP ratio high and AFP ratio low were observed in DFS and OS in both cohort ( < 0.05). Kaplan-Meier curves and receiver-operating curves were showed that AFP ratio was better than AFP level preoperation in predicting the prognosis of AFP-positive HCC patients after hepatectomy. The multivariate analysis demonstrated that AFP ratio was a significant independent risk factor for both OS and DFS in HCC patients with AFP-positive.
CONCLUSIONS
AFP ratio might be a prognosis predictor for HCC patients with AFP-positive after hepatectomy.
Topics: Carcinoma, Hepatocellular; Hepatectomy; Humans; Liver Neoplasms; Prognosis; Retrospective Studies; Survival Rate; alpha-Fetoproteins
PubMed: 35059044
DOI: 10.1155/2022/7640560 -
Annals of Hepatology 2022Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with... (Review)
Review
Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Disease Management; Humans; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Risk Factors; alpha-Fetoproteins
PubMed: 34929349
DOI: 10.1016/j.aohep.2021.100654 -
World Journal of Surgical Oncology Oct 2022The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high...
BACKGROUND
The prognosis of hepatocellular carcinoma (HCC) varies considerably among patients with the same disease stage and characteristics, and only about two thirds show high levels of α-fetoprotein (AFP), a common prognostic indicator for HCC. Here, we assessed whether the combination of presurgical serum levels of AFP and carbohydrate antigen 19-9 (CA19-9) can predict the prognosis of HCC patients after hepatectomy.
METHODS
The clinicopathological characteristics and post-hepatectomy outcomes of 711 HCC patients were retrospectively reviewed. The patients were classified into three groups based on whether their preoperative serum levels of both AFP and CA19-9 were higher than the respective cut-offs of 400 ng/ml and 37 U/ml [double positive (DP)], the level of only one marker was higher than the cut-off [single positive (SP)], or neither level was higher than the cut-off [negative (N)]. The overall survival (OS) and recurrence-free survival (RFS) rates were estimated using Kaplan-Meier curves. Univariate and multivariate survival analyses were performed to identify the clinicopathological factors significantly associated with HCC prognosis.
RESULTS
The 1-year, 3-year, and 5-year RFS and OS rates in the N group were significantly higher than those in the SP group, while the DP group showed the lowest rates. Multivariate Cox regression analysis showed that large tumor size (> 5 cm), multiple tumors (≥ 2), incomplete tumor capsule, positive microvascular invasion, Barcelona Clinic Liver Cancer C stage, and CA19-9 level > 37 U/mL were independent risk factors for RFS and OS in HCC patients. Moreover, aspartate aminotransferase levels > 40 U/L proved to be an independent prognostic factor for OS.
CONCLUSION
The combination of serum AFP and CA19-9 levels may be a useful prognostic marker for HCC patients after hepatectomy.
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Hepatectomy; CA-19-9 Antigen; Prognosis; Liver Neoplasms; Retrospective Studies; Aspartate Aminotransferases; Carbohydrates
PubMed: 36258212
DOI: 10.1186/s12957-022-02806-9