The Utility of Serum Alpha-fetoprotein for Monitoring for Relapse of Alpha-fetoprotein-Positive Hepatoblastoma.

Hepatoblastoma is the most common liver malignancy in children. Treatment typically involves surgery and cisplatin-based chemotherapy. After therapy completion, children undergo repetitive surveillance imaging to screen for relapse, which occurs in <12% of cases. Monitoring for relapse has gradually shifted to serial determination of serum alpha-fetoprotein (AFP) alone as most cases have AFP elevation at the time of relapse. Little primary data supports, such a practice, however, and herein we present both our institutional experience with relapsed hepatoblastoma and a careful review of published literature on this topic. While serial AFP monitoring may suffice for most patients, certain clinical characteristics should give pause to the practitioner, when considering posttreatment monitoring with serum AFP alone.

Ratiometric electrochemical immunoassay based on 2D Co/Fe MOF decorated with toluidine blue and Fc-labeled Schiff base for accurate assay of alpha-fetoprotein in clinical serum.

The high level of alpha-fetoprotein (AFP) expression is closely related to hepatocellular carcinoma (HCC). Herein, a dual signal ratiometric electrochemical immunosensor based on chitosan-ferrocenecarboxaldehyde-spindle gold (Chit-Fc-SAu) and Co/Fe metal-organic framework-toluidine blue/polydopamine (Co/Fe MOF-TB/PDA) was proposed for quantitative analysis of AFP. Specifically, Chit-Fc-SAu worked as a substrate to trap more primary antibodies (Ab1) generating the first electrochemical signal from Fc. Thanks to the large specific surface area, the synergistic and electronic effects of Co/Fe MOF nanosheets, and the rich functional groups of PDA, Co/Fe MOF-TB/PDA could load more secondary antibodies (Ab2) and signal molecules (TB) providing another amplified electrochemical signal. In the presence of AFP, Ab1-AFP-Ab2 formed a sandwich structure, and as the AFP concentration increased, the peak current ratio of TB to Fc (ITB/IFc) also increased. The dual signal ratiometric strategy can avoid environmental signal interference and achieve signal self-calibration, thereby improving the accuracy and reproducibility of detection. After a series of exploration, this self-calibrated ratiometric immunosensor exhibited a wide linear range (0.001-200 ng mL-1), a low detection limit (0.34 pg mL-1), and good repeatability. When applied to the assay of clinical serum samples, the detection results of ratiometric sensor were consistent with that of commercial electrochemiluminescence (ECL) immunoassay, significantly superior to that of non-ratiometric sensor. The self-calibrated strategy based on ratiometric sensor helps to improve the accuracy of AFP in clinical diagnosis.

Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

Volatile organic compounds for diagnosis of early hepatocellular carcinoma in at-risk patients.

BACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC. METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP). RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis. CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.

Transcriptomic Signature of 3D Hierarchical Porous Chip Enriched Exosomes for Early Detection and Progression Monitoring of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non-invasive diagnosis method based on serum markers, such as α-fetoprotein (AFP), and des-γ-carboxy-prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere-coated three-dimensional (3D) hierarchical porous chip, named a SiO2-chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non-HCC and HCC subjects are enriched using an SiO2-chip and performed RNA sequencing to identify HCC-related long non-coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT-1 and EGFR-AS-1 are two HCC-related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT-PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy-based approach for noninvasive and reliable HCC detection is developed.

Alpha-fetoprotein level in fetuses, infants, and children with ovarian masses: a literature 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.

Electrochemiluminescent resonance energy transfer between amino-modified g-C3N4/Bi2MoO6 composite and carboxyl CoS2 nanoboxes for sensitive detection of alpha fetoprotein.

This work demonstrates an effective quenching electrochemiluminescent (ECL) immunosensor based on resonance energy transfer for the sensitive detection of alpha fetoprotein (AFP). In this strategy, graphitic carbon nitride (g-C3N4) was coupled with bismuth molybdenum oxide (Bi2MoO6) to form a g-C3N4/Bi2MoO6 nanocomposite as a novel type of ECL immunosensor. The as-synthesized amino-modified g-C3N4/Bi2MoO6 nanocomposite presents strong and stable cathodic ECL activity compared to pristine g-C3N4. One plausible reason is that the synergistic effect between the g-C3N4 and Bi2MoO6 could facilitate charge transfer process and thereby enhancing the separation efficiency of electron-hole pairs. The other functional part of the immunosensor, carboxyl CoS2 nanoboxes with a broad absorption range, was rationally designed and introduced. The evidence that the absorption spectra of carboxyl CoS2 NBs overlap with ECL spectra of g-C3N4/Bi2MoO6 nanocomposite holds accountable for exceptionally weakened ECL signal. This sandwich-type immunosensor was setup based on quenching mechanism concerning amino-modified g-C3N4/Bi2MoO6 as an ECL donor and carboxyl CoS2 NBs as an ECL accepter. The strategy was optimized to achieve a convincible and sensitive detection goal for AFP with a wide quantifiable range of 0.5 pg/mL-10 ng/mL whilst a sufficiently low detection limit of 0.04 pg/mL (S/N = 3). This immunosensor shows great potential for real sample analysis with reasonable recoveries ranging from 95.5 to 99.0 %, demonstrating its high precision for AFP determination.

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.

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.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong.

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.

A novel microfluidic chip integrating with microcolumn array electrodes for rapid and ultrasensitive detection of alpha-fetoprotein.

BACKGROUND: Cancer posed a serious threat to human health, and early diagnosis of cancer biomarker was extremely important for the treatment and control of cancer. Electrochemistry-based assays were low-cost, responsive and easy to operate, but there were some challenges in terms of accuracy, detection limit, efficiency and portability. The combination of microfluidic devices and electrochemical methods was expected to construct a high-performance sensing platform, but long-time antigen-antibody incubation was still required. Therefore, a novel microfluidic chip needs to be developed, which has the advantages of good portability, short incubation time, high accuracy, low detection limit and great application to point-of-care testing. RESULTS: A microfluidic sensor based on microcolumn array electrodes was developed, in which microcolumns could create local mixed flow to reduce the incubation time of target molecules and enhance their interaction with the sensing interface. Besides, three dimensional Mxene fibers-gold nanoparticles (3D MF-Au) was modified on the microcolumn array electrodes to increase active sites and provide more electrolyte shuttle holes. The electrolyte turbulence caused by the microcolumn array electrodes could heighten the contact between the target molecules and sensing interface and accelerate the transfer of redox pairs, thus reducing the incubation time of the target molecules and improving the electrochemical responses in synergy with the 3D MF-Au. Herein, the detection of AFP was chosen as a model, and the microfluidic sensor possessed superior performance for analysis of AFP in the range of 0.1 pg mL-1 - 200 ng mL-1 with a low detection limit (LOD) of 0.0648 pg mL-1. SIGNIFICANCE: This microfluidic chip integrating with microcolumn array electrodes has been successfully implemented to detect AFP in human serum, and the results were consistent with that of electrochemical chemiluminescence method. The microfluidic chip provided a new strategy of portability, shortening incubation time and enhancing electrical signals for antigen detection of real samples, which showed great utilization potentiality in point-of-care testing.

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases.

Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.

Transistor-based immunosensor using AuNPs-Ab2-HRP enzyme nanoprobe for the detection of antigen biomarker in human blood.

Alpha-fetoprotein (AFP) is inextricably linked to various diseases, including liver cancer. Thus, detecting the content of AFP in biology has great significance in diagnosis, treatment, and intervention. Motivated by the urgent need for affordable and convenient electronic sensors in the analysis and detection of aqueous biological samples, we combined the solution-gated graphene transistor (SGGT) with the catalytic reaction of enzyme nanoprobes (HRP-AuNPs-Ab2) to accurately sense AFP. The SGGT immunosensor demonstrated high specificity and stability, excellent selectivity, and excessive linearity over a range of 4 ng/mL to 500 ng/mL, with the lower detection limit down to 1.03 ng/mL. Finally, clinical samples were successfully detected by the SGGT immunosensor, and the results were consistent with chemiluminescence methods that are popular in hospitals for detecting AFP. Notably, the SGGT immunosensor is also recyclable, so it has excellent potential for use in high-throughput detection.

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.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We recorded imaging receipt in the year before HCC diagnosis: ultrasound plus α-fetoprotein (AFP), ultrasound alone, multiphasic contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI), and no liver imaging. We used multivariable logistic and Cox regression analysis to compare early tumor detection, curative treatment receipt, and overall survival between surveillance strategies. RESULTS: Among 2028 patients with HCC (46.7% Barcelona Clinic Liver Cancer stage A), 703 (34.7%) had ultrasound plus AFP, 293 (14.5%) had ultrasound alone, 326 (16.1%) had multiphasic CT/MRI, and 706 (34.8%) had no imaging in the year before HCC diagnosis. Over the study period, proportions without imaging were stable, whereas use of CT/MRI increased. Compared with no imaging, CT/MRI and ultrasound plus AFP, but not ultrasound alone, were associated with early stage HCC detection and curative treatment. Compared with ultrasound alone, CT/MRI and ultrasound plus AFP were associated with increased early stage detection. CONCLUSIONS: HCC surveillance patterns vary in clinical practice and are associated with differing clinical outcomes. While awaiting data to determine if CT or MRI surveillance can be performed in a cost-effective manner in selected patients, AFP has a complementary role to ultrasound-based surveillance, supporting its adoption in practice guidelines.

Value Analysis of Four-Dimensional Color Ultrasound Combined with Maternal Serological Index in Prenatal Screening for Fetal Anomalies.

Objective: This study aimed to assess the efficacy of combining four-dimensional (4D) color ultrasound with maternal serological index testing in prenatal screening for fetal anomalies. Methods: A retrospective analysis was conducted on data from 864 pregnant women who underwent prenatal checkups at the hospital between January 2020 and January 2021. During the mid-pregnancy period, serological tests were performed to determine levels of alpha-fetoprotein (AFP), free ß-subunit of human chorionic gonadotropin (Free-HCG ß), pregnancy-associated plasma protein A (PAPP-A), and vitamin B12 (VitB12). Additionally, 4D color ultrasound examinations were conducted. The gold standard for evaluation was the results of delivery or labor induction. AFP, Free-HCG ß, PAPP-A, and VitB12 levels were compared between the anomaly group and the normal group. The diagnostic efficacy of single and combined detection of serological indexes and 4D color ultrasound was analyzed, with the calculation of the areas under the curve (AUC) for different detection methods. Results: Among the 864 pregnant women, 44 cases (5.09%) exhibited fetal anomalies, while 820 cases (94.91%) did not. The anomaly group showed significantly higher multiples of the median (MOM) values for AFP and Free-HCG ß (P < .001) and significantly lower PAPP-A MOM and VitB12 levels (P < .001) compared to the normal group. The sensitivity of single detections for AFP MOM, Free-HCG ß MOM, PAPP-A MOM, VitB12, 4D color ultrasound, and combined detection were 63.64%, 68.18%, 65.91%, 54.55%, 77.27%, and 97.93%, respectively. The corresponding AUC values were 0.805, 0.829, 0.818, 0.761, 0.885, and 0.974. Conclusions: The combination of 4D color ultrasound with maternal serological index testing demonstrated high sensitivity in prenatal screening for fetal anomalies.

Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with one of the highest cancer-related mortality rates worldwide. Early diagnosis is crucial for improving the therapeutic options and reducing the disease-related mortality. AIM: To investigate serum N-glycomics as diagnostic markers for HCC. METHODS: We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N-glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers. RESULTS: Of the 48 articles included, 11 evaluated the utility of N-glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha-fetoprotein (AFP), kininogen (Kin), α-1-antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post-translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics-based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92-0.97. However, these were based on single studies with limited sample sizes and should therefore be validated. CONCLUSIONS: Alterations in serum N-glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible.

Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.

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.

Lysosomes Initiating and DNAzyme-Assisted Intracellular Signal Amplification Strategy for Quantification of Alpha-Fetoprotein in a Single Cell.

Cellular trace proteins are critical for maintaining normal cell functions, with their quantitative analysis in individual cells aiding our understanding of the role of cell proteins in biological processes. This study proposes a strategy for the quantitative analysis of alpha-fetoprotein in single cells, utilizing a lysosome microenvironment initiation and a DNAzyme-assisted intracellular signal amplification technique based on electrophoretic separation. A nanoprobe targeting lysosomes was prepared, facilitating the intracellular signal amplification of alpha-fetoprotein. Following intracellular signal amplification, the levels of alpha-fetoprotein (AFP) in 20 HepG2 hepatoma cells and 20 normal HL-7702 hepatocytes were individually evaluated using microchip electrophoresis with laser-induced fluorescence detection (MCE-LIF). Results demonstrated overexpression of alpha-fetoprotein in hepatocellular carcinoma cells. This strategy represents a novel technique for single-cell protein analysis and holds significant potential as a powerful tool for such analyses.

Proteome microarray identifies autoantibody biomarkers for diagnosis of hepatitis B-related hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) has the highest mortality rate among malignant tumors worldwide. This study aimed to analyze the biological characteristics of serum proteins in hepatitis B (HBV)-related liver diseases, identify diagnostic biomarkers for HBV-infected HCC, and provide a scientific basis for its prevention and treatment. MATERIALS AND METHODS: We used HuProt arrays to identify candidate biomarkers for HBV-related liver diseases and verified the differential biomarkers by using an HCC-focused array. The biological characteristics of serum proteins were analyzed via bioinformatics. Serum biomarkers levels were validated by ELISA. RESULTS: We identified 547 differentially expressed proteins from HBV-infected HCC in a screening cohort. After analyzing the biological characteristics of serum proteins, we identified 10 potential differential autoantibodies against tumor-associated antigens (TAAbs) and a candidate biomarker panel (APEX2, RCSD1, and TP53) for the diagnosis of HBV-associated HCC with 61.9% sensitivity and 81.7% specificity in an HCC-focused array validation cohort. Finally, the protein levels and diagnostic capability of the biomarker panel were confirmed in a large-sample validation cohort, and this panel was found to be superior to alpha-fetoprotein, the standard hallmark for the diagnosis of HCC. CONCLUSION: The APEX2, RCSD1, and TP53 biomarker panels could be used for the diagnosis of HBV-associated HCC, providing a scientific basis for clinical practice.