Alpha-fetoprotein Research Articles

Pronounced signal enhancement with gourd-shaped hollow PtCoNi bunched nanochains for electrochemical immunosensing of alpha-fetoprotein

Alpha-fetoprotein (AFP) is a vital biomarker for hepatocellular carcinoma (HCC), whose accurate analysis is essential to early diagnosis and prognosis. Herein, gourd-shaped hollow PtCoNi bunched nanochains (GH-PtCoNi BNCs) were synthesized in oleylamine under solvothermal condition coupled by acidic etching. The resulting GH-PtCoNi BNCs showed significantly enlarged specific surface area and exceptional electrocatalytic activity, as manifested by benchmarked hydrogen peroxide (H2O2) reduction, benefiting for label-free electrochemical immunoanalysis of AFP. The analytical characterizations were evaluated by a set of techniques such as chronoamperometry, cyclic voltammetry (CV), etc. The as-built biosensor displayed a broader linear range of 0.1 ∼ 105 pg mL−1 and a lower limit of detection down to 0.017 pg mL−1 in the optimized surroundings, integrated by detection of AFP in human serum samples with acceptable results. This study shows some constructive insights for development of advanced nanomaterials and applications in early diagnostics.

Upfront or delayed surgery in resectable hepatoblastoma: analysis from the children’s hepatic tumors international collaboration database

In the treatment of resectable hepatoblastoma (HB), it has not been established whether upfront surgery (UF) at diagnosis or neoadjuvant chemotherapy and delayed surgery (DL) is preferred. We compared patients with localized HB who underwent either UF, or DL after neoadjuvant chemotherapy in the Children's Hepatic tumors International Collaboration (CHIC) database of 1605 cases enrolled in eight multicenter hepatoblastoma trials between 1988 and2010. Among the 512 resectable HB patients who had PRETEXT (PRETreament EXTent of disease) I or II unruptured tumors at diagnosis without extrahepatic invasion, distant metastases, or massive vascular invasion, 172 underwent UF and 340 underwent DL. The primary outcomes were event-free and overall survivals after start of treatment in these two groups. Survival analysis was performed using the Kaplan-Maier analysis with long-rank tests and multivariable Cox regression models. Complete resection rates were comparable (93.6% in UF and 89.7% in DL). The total cycles of chemotherapy of DL (median:6) were significantly more than those of UF (median:4) (P<0.01). The 5-year event-free survival (EFS) was 90.6% and 86.6% (P=0.89) in the UF and DL cohorts, respectively. The surgical complications, recurrence rates, and late complications were not significantly different between the cohorts but the EFS rates of DL patients with a low alpha-fetoprotein (AFP) level (100-999ng/mL) or older age at diagnosis (≥3 years old) were significantly worse than others. The outcomes, surgical resectability, and complications were not significantly different between the UF and DL groups. Eligible patients with a low AFP level (<1000ng/mL) or older age (≥3 years old) showed better outcomes in the UF group and might be considered for initial resection. European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission; Children's Oncology Group Cure Search grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research and Development; Japan Society for the Promotion of Science; and Swiss Cancer Research grant.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Primary yolk sac tumor of the endometrium combined with situs inversus totalis: a case report and literature review

BackgroundYolk sac tumor (YST) is a highly malignant germ cell tumor, a majority of which originate from the gonads and are extremely rare from endometrium.Case presentationHere we present a case of a 42-year-old woman suffered from primary pure yolk sac tumor of the endometrium complicated with situs inversus totalis. The patient presented at our hospital with irregular vaginal bleeding. Imageological examination showed a space-occupying lesion in the cervix and the serum Alpha-fetoprotein (AFP) level was significantly high (more than 1210ng/ml). Then she underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. The subsequent postoperative pathological diagnosis was yolk sac tumor arising from the endometrium. Next, the patient was treated with 6 cycles of chemotherapy with Pingyangmycin, etoposide and cisplatin regimen and was alive without evidence of recurrence or distant metastases for 13 months.ConclusionsThis rare disease needs to be differentiated from endometrial epithelial neoplasia and the significant increase in AFP is helpful for diagnosis. Combined with previous literature reports, comprehensive staging laparotomy or maximum cytoreductive surgery complemented by standard chemotherapy can usually achieve a good efficacy.

Prognostic nomogram of overall survival for radiation therapy in hepatocellular carcinoma: a population study based on the SEER database and an external cohort.

Radiotherapy (RT) plays an important role in the treatment of hepatocellular carcinoma (HCC). To screen patients who benefit most from RT, a nomogram for survival prediction of RT based on a large sample of patients with HCC was created and validated. A total of 2,252 cases collected from the Surveillance, Epidemiology, and End Results (SEER) database were separated into a training or an internal validation cohort in a 7:3 ratio (n = 1,565:650). An external validation cohort of cases from our institute was obtained (n = 403). LASSO regression and Cox analyses were adopted to develop a nomogram for survival prediction. The decision curve analysis (DCA), calibration curve, and time-dependent receiver operating characteristic curves (TROCs) demonstrated the reliability of the predictive model. For patients with HCC who received RT, the analyses revealed that the independent survival prediction factors were T stage {T2 vs. T1, hazard ratio (HR) =1.452 [95% CI, 1.195-1.765], p < 0.001; T3 vs. T1, HR = 1.469 [95% CI, 1.168-1.846], p < 0.001; T4 vs. T1, HR = 1.291 [95% CI, 0.951-1.754], p = 0.101}, N stage (HR = 1.555 [95% CI, 1.338-1.805], p < 0.001), M stage (HR = 3.007 [95% CI, 2.645-3.418], p < 0.001), max tumor size (>2 and ≤5 vs. ≤2 cm, HR = 1.273 [95% CI, 0.992-1.633], p = 0.057; >5 and ≤10 vs. ≤2 cm, HR = 1.625 [95% CI, 1.246-2.118], p < 0.001; >10 vs. ≤2 cm, HR = 1.784 [95% CI, 1.335-2.385], p < 0.001), major vascular invasion (MVI) (HR = 1.454 [95% CI, 1.028-2.057], p = 0.034), alpha fetoprotein (AFP) (HR = 1.573 [95% CI, 1.315-1.882], p < 0.001), and chemotherapy (HR = 0.511 [95% CI, 0.454-0.576], p < 0.001). A nomogram constructed with these prognostic factors demonstrated outstanding predictive accuracy. The area under the curve (AUC) in the training cohort for predicting overall survival (OS) at 6, 12, 18, and 24 months was 0.824 (95% CI, 0.803-0.846), 0.824 (95% CI, 0.802-0.845), 0.816 (95% CI, 0.792-0.840), and 0.820 (95% CI, 0.794-0.846), respectively. The AUCs were similar in the other two cohorts. The DCA and calibration curve demonstrated the reliability of the predictive model. For patients who have been treated with RT, a nomogram constructed with T stage, N stage, M stage, tumor size, MVI, AFP, and chemotherapy has good survival prediction ability.

Validity of predictive score model for microvascular invasion in hepatocellular carcinoma.

Objective: To validate a risk score model to predict MVI using Total tumor volume (TTV) and AFP. Study Design: Cross-sectional. Setting: Department of Gastroenterology, Liaquat National Hospital, Karachi, Pakistan. Period: June 2022 to December, 2023. Methods: Patients of either gender, older than 18 years and above with confirmed diagnosis of HCC were enrolled. When there were several HCC tumors, the largest tumor's axis was measured and used as the representative HCC diameter. When microscopic tumor invasion was detected in the portal, hepatic vein, or biliary vein of the surrounding liver tissue that was adjacent to the tumor, it was referred to as micro vascular invasion. Results: Total 302 patients were studied with mean age of 62.1 ± 9.2 years. Majority of patients were males (64.2%). Around one-fifth patients had more than one tumor (19.9%). Out of 302 patients, MVI was seen in 30.1% patients. In multivariable analysis number of tumors (aOR=220.65, 95% CI: 128.91-922.67), tumor volume (aOR=1.01, 95% CI: 1.01-1.02), and AFP (aOR=1.01, 95% CI: 1-1.02) were found to be significant predictors of MVI. Conclusion: This study validated a prediction model for forecasting of MVI in HCC patients with highly significant variables including number of tumors, tumor volume and alpha feto protein. Timely decision making could be done using this model.

Potential Diagnostic Role of Serum Fibroblast Growth Factor-19 in Hepatocellular Carcinoma.

A highly accurate diagnostic method is crucial to reduce mortality and increase hepatocellular carcinoma (HCC) survival. Current biomarkers have limited accuracy, and novel ones are needed. Fibroblast growth factor-19 (FGF-19) is overexpressed in HCC. This study aimed to assess FGF-19 as a potential novel diagnostic biomarker for HCC. This case-control study involved 114 individuals divided into three equal groups: HCC (n=38), Cirrhosis (n=38), and Control (n=38). HCC biomarkers included alpha-fetoprotein (AFP), Des-γ-carboxy prothrombin (DCP), and FGF-19. The three markers, FGF-19, DCP, and AFP, were significantly different between the three groups, except that DCP was comparable between HCC and Cirrhosis groups (p=1.000). All individuals in the control group had FGF-19 levels below the minimum level in the HCC group. Thus, FGF-19 had 100% sensitivity and specificity in differentiating HCC from healthy controls. FGF-19 can discriminate between HCC and Cirrhosis groups at a 140.8 pg/mL cutoff with sensitivity and specificity of 81.8% and 87.9%, respectively. The sensitivity of FGF-19 was higher than AFP, trending toward statistical significance (p=0.095). Combining FGF-19 with AFP, DCP, or both improved sensitivity but decreased specificity. FGF-19 is a possible noninvasive serum biomarker for HCC. Its combination with AFP or DCP improves the sensitivity for detecting HCC.

The role of IQCB1 in liver cancer: a bioinformatics analysis.

Liver hepatocellular carcinoma (LIHC) is a prevalent malignancy globally, exhibiting substantial incidence and mortality rates. Early diagnosis and prevention of metastasis are crucial for the benefit of patients with liver cancer. The present study aimed to elucidate the involvement of IQCB1 in liver cancer through the utilization of bioinformatics. The samples utilized in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Initially, the TCGA-LIHC dataset was employed to examine the expression of IQCB1, and its validation was performed on the GSE25097 dataset. Subsequently, Kaplan-Meier (KM) analysis was conducted to evaluate the prognostic significance of IQCB1 in LIHC, and its correlation with clinical pathological features was also investigated. Furthermore, a protein-protein interaction (PPI) network consisting of 20 proteins associated with IQCB1 was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. A risk model was formulated to assess the prognostic significance and its prognostic value was compared to that of IQCB1 in isolation. Furthermore, an examination was conducted to explore the correlation between IQCB1 and immune infiltration, along with the involvement of immunological checkpoints. A drug sensitivity assessment of IQCB1 was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Additionally, the Tumor Immune Single-cell Hub (TISCH) database was utilized to investigate the association between IQCB1 and the tumor microenvironment (TME). The expression of IQCB1 was observed to be significantly elevated in tumor samples. Furthermore, patients with high expression levels of IQCB1 demonstrated a poorer prognosis. Additionally, IQCB1 exhibited significant correlations with MKI67, hepatitis B virus (HBV), hepatitis C virus (HCV), and alpha-fetoprotein (AFP). GO and KEGG analyses revealed enrichment of multiple signaling pathways. Subsequently, an investigation was conducted to examine the association between IQCB1 and the activity of ten signaling pathways related to tumor development. A positive correlation was observed between IQCB1 expression and T-helper 2 (Th2) cells, whereas a negative correlation was observed between IQCB1 expression and Th17 cells. Furthermore, a positive association was found between IQCB1 and immune checkpoints, particularly with CD276. Analysis of single-cell data from the TISCH database revealed widespread expression of IQCB1 in the TME. Additionally, screening revealed that among 12 drugs related to IQCB1, a subset of 10 drugs demonstrated negative correlations, whereas two drugs exhibited positive correlations. IQCB1 has the potential to function as a diagnostic and prognostic molecular marker, and its association with immune infiltration and checkpoint mechanisms has been observed.

Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

Comparison of Local Recurrence Between LEN-TACE and TACE for Hepatocellular Carcinoma According to Lipiodol Accumulation.

Transarterial chemoembolization (TACE) is the standard treatment for patients with hepatocellular carcinoma in the intermediate stage; however, with advances in systemic therapy, the indications for TACE have gained significance. While lenvatinib (LEN)-TACE offers the potential for good outcomes, local recurrence has not yet been adequately investigated. Therefore, this study investigated local recurrence factors for each type of TACE, focusing on the lipiodol (Lip) value in LEN-TACE and conventional TACE. Fifty patients (50 nodes) with hepatocellular carcinoma and a tumor size <7 cm who underwent LEN-TACE or TACE between January 2022 and June 2023 were included in this study to investigate local recurrence and its influencing factors. The local recurrence rate after LEN-TACE was 5.6% at 6 months and 11.5% at 12 months, whereas those after TACE were 6.4% at 6 months and 13.2% at 12 months (p=0.028). There were no significant differences in local recurrence rates according to background liver factors, alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) values, sex, age, and albumin-bilirubin (ALBI) score. Lipiodol (Lip) values immediately after LEN-TACE were significantly higher than those after TACE alone (p=0.021). Multivariate analysis showed that LEN-TACE had a recurrence hazard ratio of 0.184. LEN-TACE provided good local tumor control. Local recurrence factors included LEN pretreatment, and Lip CT values were higher immediately after LEN-TACE. Thus, LEN-TACE after upfront LEN administration may increase the effectiveness of TACE.

Hepatic Arterial Infusion Chemotherapy Combined Lenvatinib and PD-1 Inhibitor Showed Improved Survival for Infiltrative Hepatocellular Carcinoma: A Multicenter Cohort Study.

Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC. A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score-matching (PSM). The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs). Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.

Analysis of Risk Factors Associated with Gestational Diabetes Mellitus: A Retrospective Case-Control Study.

Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM. A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed. The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥30 years old, body mass index (BMI) in early pregnancy≥24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥30 years old (≥30 vs <30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183-3.878, p=0.012), BMI≥24.0 kg/m2 (≥24.0 kg/m2 vs 18.5-23.9 kg/m2, OR: 1.887, 95% CI: 1.041-3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022-3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046-7.863, p=0.041) were associated with GDM. Age of pregnant woman ≥30 years old, BMI≥24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.

A Route to the Colorimetric Detection of Alpha-Fetoprotein Based on a Smartphone.

Alpha-fetoprotein (AFP) is a key marker for early cancer detection and assessment. However, the current detection methods struggle to balance accuracy with the need for decentralized medical treatment. To address this issue, a new AFP analysis platform utilizing digital image colorimetry has been developed. Functionalized gold nanoparticles act as colorimetric agents, changing from purple-red to light gray-blue when exposed to different AFP concentrations. A smartphone app captures these color changes and calculates the AFP concentration in the sample. To improve detection accuracy, a hardware device ensures uniform illumination. Testing has confirmed that this system can quantitatively analyze AFP using colorimetry. The limit of detection reached 0.083 ng/mL, and the average accuracy reached 90.81%. This innovative method enhances AFP testing by offering portability, precision, and low cost, making it particularly suitable for resource-limited areas.

Clinical, Biochemical, and Molecular Characteristics of Filipino Patients with Tyrosinemia Type 1.

Hereditary tyrosinemia type I (HT1), or hepatorenal tyrosinemia, is an amino acid disorder which may cause hepatic failure as well as renal and neurologic comorbidities. Early detection of this disorder is possible with newborn screening (NBS). The objective of this study is to describe the clinical, biochemical, and molecular characteristics of Filipino patients diagnosed with HT1 through the expansion of the Philippine NBS program in 2014. There were a total of 16 patients with confirmed HT1 from then until September 2022. Clinical and biochemical data during confirmation and initial evaluation, as well as molecular data, were obtained from the patients' medical records. The cohort included children between the ages of 18 and 54 months at the time of data collection. The mean age at treatment initiation was 26.8 days. The mean succinylacetone level from dried blood spot sampling using tandem mass spectrometry (MS) was 11.1 µmol/L. Biochemical confirmatory tests via plasma amino acid analysis showed mean levels of tyrosine, phenylalanine, and methionine of 506.1 µmol/L, 111.5 µmol/L, and 125.4 µmol/L, respectively. Upon urine organic acid (UOA) analysis, succinylacetone was detected in all except for one patient, who was managed prior to UOA analysis. The most common clinical characteristics were abnormal clotting times (62.5%), elevated alpha fetoprotein (37.5%), anemia (31.3%), and metabolic acidosis (31.3%). The most common genotype was homozygous c.122T>C p.Leu41Pro in 64.3% of patients. The allelic frequency of this pathogenic variant is 71.4%. The inclusion of HT1 in the Philippine NBS program allowed early diagnosis and management of HT1 patients.

The Value of Human Epididymal Protein 4, Carcinoembryonic Antigen and Alpha-Fetoprotein in the Early Diagnosis of Cervical Cancer

Objectives: This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. Design: This was a clinical study. Participants: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. Setting: The review was conducted in a Jiaxing First Hospital. Methods: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with CIN (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA, and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA, and AFP and the clinicopathological characteristics of patients with early stage cervical cancer were analyzed, and the receiver operating characteristic (ROC) curves were plotted to identify the value of the single and triple tests of serum HE4, CEA, and AFP for the early stage diagnosis of cervical cancer. Results: The levels of serum HE4, CEA, and AFP in the early stage cervical cancer group were higher than those in the disease control and the healthy control groups (p < 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early stage cervical cancer (p < 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early stage cervical cancer were 0.725, 0.679, 0.663, and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (p < 0.05). Limitations: There is a lack of larger sample sizes to test whether the combined HE4, CEA, and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV-DNA detection and compare it with the levels of serum markers. Conclusion: The combination of HE4, CEA, and AFP has good clinical reference value analysis in the auxiliary diagnosis of early stage cervical cancer, and it is worthy of further validation and popularization.

Development of an indirect ELISA to detect antigens using DNA origami nanoantenna labeled specific monoclonal antibodies

This research examines the development of an indirect ELISA to detect antigens using DNA origami nanoantenna-labeled specific monoclonal antibodies. Hepatocellular carcinoma (HCC) is one of the five most common cancers and the second leading cause of cancer-related death worldwide. More than 60% of cases are detected in the late stage, with the absence of specific symptoms in the early stage of the disease. Adding measurements of AFP (Alpha-Fetoprotein), TXN (Thioredoxin), and DCP (Des-γ-Carboxy Prothrombin) has the potential to improve the accuracy of diagnosing hepatocellular carcinoma. DNA origami technology is revolutionizing the forefront of cancer diagnostics, particularly for HCC. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) method targeting the assessment of the effectiveness of specific monoclonal antibody-conjugated DNA origami particles was developed. The results of DNA origami folding into complex nanostructures and labeled biomarkers like AFP, DCP, and TXN have explored the high specificity and sensitivity for targeting HCC. We found the cut-off values for AFP, DCP, and TXN to be 0.132, 0.156, and 0.150, respectively. The coefficients of variation for samples remained consistently under 10%, indicating the method's high degree of stability and reproducibility. This innovation, combined with biomarkers, promised in early HCC detection, holds the potential to significantly enhance patient outcomes in the fight against liver cancer. The platform also has enormous potential for advancing personalized medicine.

Association of serum alpha-fetoprotein (AFP) with indirect prognosis in gastric cancer

Aims: Alpha-fetoprotein (AFP) is a glycoprotein secreted from the yolk sac and hepatocytes during fetal life. Elevated levels in adults are considered markers for yolk sac tumors, hepatocellular carcinoma and gastric cancer. There is still no consensus on the definition of AFP-secreting gastric cancers, but AFP-secreting gastric cancers have been reported to have a worse prognosis. In this study, AFP levels in gastric cancers with high AFP were compared with pathology results and evaluated in terms of indirect prognosis. Methods: Patients with gastric cancer operated in the General Surgery Clinic of Ankara Bilkent City Hospital between 2019 and 2023 were retrospectively screened. Among the screened patients, those whose information could not be reached and those with incomplete information were excluded and 126 patients were included in the study. Serum AFP levels of these patients were compared with pathology results, stages and tumor sizes. Results: The mean age of the patients in our study was 66±11 years, 42 (33.6%) were female and 84 (66.7%) were male. Of the 126 patients analyzed in the study, 107 (84.9%) were AFP-negative and 19 (15.1%) were AFP-positive. There was no significant difference in AFP levels between all patients in terms of liver metastasis, peritoneal metastasis, disease stage, perineural invasion and tumor location. However, serum AFP levels were significantly higher in patients with lymphovascular invasion and lung metastases (p=0.042; p=0.024). In the analysis for serum AFP level in the presence of lymphovascular invasion, ROC value was 2.35 ng/ml, sensitivity 58.2%, specificity 55.9%, area under the curve (AUC) 0.618, 95% confidence interval (95% CI) 0.512-0.723 and p=0.028. Conclusion: Lymphovascular invasion is a poor prognostic factor in gastric cancer. In this study, a significant correlation was found between serum AFP value and lymphovascular invasion. In gastric cancers without AFP secretion, a serum AFP value above 2.35 ng/ml may be indirectly associated with poor prognosis because it predicts lymphovascular invasion.

Limited Role of MSAFP Screening for Prenatal Omphalocele Detection.

Although serum screening for aneuploidies has become less prevalent, maternal-serum alpha-fetoprotein (MSAFP) screening for body-wall defects remains widespread. We explored whether MSAFP screening is associated with earlier omphalocele detection than ultrasound alone. This is a retrospective cohort study of prenatally detected omphalocele cases at our center from 2007 to 2023. We explored the association between MSAFP screening, gestational age at omphalocele detection, and clinical outcomes. Among 101 pregnancies with prenatally diagnosed omphalocele, 27 (26.7%) had MSAFP screening. The median gestational age at MSAFP screening was 17 weeks 4 days. Of those who received MSAFP screening, 11 (41%) had values ≥2.5 multiples of the median (MoM) and 16 (59%) were not elevated. MSAFP results did not correlate with omphalocele size and were not associated with prenatal or postnatal outcomes. MSAFP screening did not result in earlier suspicion for or confirmation of omphalocele (P = .97 and P = .87, respectively). In contrast, first-trimester ultrasound screening was associated with earlier suspicion for and confirmation of omphalocele (P < .01 and P = .01, respectively). There were no clinical or demographic differences between those who received MSAFP screening and those who did not (including body mass index or commute distance to an urban center). MSAFP screening is not associated with earlier omphalocele detection. Furthermore, in pregnancies with prenatally diagnosed omphalocele, the results of MSAFP screening are not predictive of clinical outcomes.

Changes in Incidence of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the United States

IntroductionHepatocellular carcinoma (HCC) occurs most often in a background of cirrhosis. Patients with noncirrhotic HCC represent a distinct population, which has been characterized in single-center studies, but has not been fully evaluated on a population level in the United States. Materials and methodsHCC cases from Surveillance, Epidemiology, and End-Results diagnosed between 2000 and 2020 were categorized as cirrhotic or noncirrhotic. Clinical and pathologic factors, age-adjusted incidence rates (AAIR), and the overall HCC-specific survival were compared between groups. ResultsThere were 18,592 patients with cirrhosis (80.4%) and 4545 without (19.6%). AAIRs for noncirrhotic HCC remained relatively unchanged from 2010 to 2020, with a mean incidence of 0.35 per 100,000. The AAIR for cirrhotic HCC declined from 1.59 to 0.85 per 100,000 during the same period. Patients with cirrhosis were younger (median age 62 versus 65 y, P < 0.001). Patients without cirrhosis, compared to those with cirrhosis, were less likely to have elevated alpha fetoprotein (53.9% versus 62.0%, P < 0.001), had larger tumors (median tumor size 5.0 versus 3.5 cm, P < 0.001), presented more frequently with localized disease (59.9% versus 55.8%, P < 0.001), were more likely to undergo surgery (OR 2.21, 95% CI 2.07-2.36), and had better HCC-specific survival (median 40 versus 27 mo, P < 0.001). ConclusionsThe relative increase in the proportion of noncirrhotic HCC in the Untied States may be due to a decline in the incidence of cirrhotic HCC. Patients with noncirrhotic HCC have larger tumors, are more likely to undergo surgical resection, and have improved cancer-specific survival.

Leveraging SEER data through machine learning to predict distant lymph node metastasis and prognosticate outcomes in hepatocellular carcinoma patients.

This study aims to develop and validate machine learning-based diagnostic and prognostic models to predict the risk of distant lymph node metastases (DLNM) in patients with hepatocellular carcinoma (HCC) and to evaluate the prognosis for this cohort. Utilizing a retrospective design, this investigation leverages data extracted from the Surveillance, Epidemiology, and End Results (SEER) database, specifically the January 2024 subset, to conduct the analysis. The study cohort consists of 15,775 patients diagnosed with HCC as identified within the SEER database, spanning 2016 to 2020. In the construction of the diagnostic model, recursive feature elimination (RFE) is employed for variable selection, incorporating five critical predictors: age, tumor size, radiation therapy, T-stage, and serum alpha-fetoprotein (AFP) levels. These variables are the foundation for a stacking ensemble model, which is further elucidated through Shapley Additive Explanations (SHAP). Conversely, the prognostic model is crafted utilizing stepwise backward regression to select pertinent variables, including chemotherapy, radiation therapy, tumor size, and age. This model culminates in the development of a prognostic nomogram, underpinned by the Cox proportional hazards model. The outcome of the diagnostic model is the occurrence of DLNM in patients. The outcome of the prognosis model is determined by survival time and survival status. The integrated model developed based on stacking demonstrates good predictive performance and high interpretative variability and differentiation. The area under the curve (AUC) in the training set is 0.767, while the AUC in the validation set is 0.768. The nomogram, constructed using the Cox model, also demonstrates consistent and strong predictive capabilities. At the same time, we recognized elements that have a substantial impact on DLNM and the prognosis and extensively discussed their significance in the model and clinical practice. Our study identified key predictive factors for DLNM and elucidated significant prognostic indicators for HCC patients with DLNM. These findings provide clinicians with valuable tools to accurately identify high-risk individuals for DLNM and conduct more precise risk stratification for this patient subgroup, potentially improving management strategies and patient outcomes.