Alpha-fetoprotein Research Articles

Exploring novel circulating biomarkers for liver cancer through extracellular vesicle characterization with infrared spectroscopy and plasmonics

BackgroundHepatocellular carcinoma (HCC) is the most common form of liver cancer, with cirrhosis being a major risk factor. Traditional blood markers like alpha-fetoprotein (AFP) demonstrate limited efficacy in distinguishing between HCC and cirrhosis, underscoring the need for more effective diagnostic methodologies. In this context, extracellular vesicles (EVs) have emerged as promising candidates; however, their practical diagnostic application is restricted by the current lack of label-free methods to accurately profile their molecular content. To address this gap, our study explores the potential of mid-infrared (mid-IR) spectroscopy, both alone and in combination with plasmonic nanostructures, to detect and characterize circulating EVs. ResultsEVs were extracted from HCC and cirrhotic patients. Mid-IR spectroscopy in the Attenuated Total Reflection (ATR) mode was utilized to identify potential signatures for patient classification, highlighting significant changes in the Amide I-II region (1475-1700 cm−1). This signature demonstrated diagnostic performance comparable to AFP and surpassed it when the two markers were combined. Further investigations utilized a plasmonic metasurface suitable for ultrasensitive spectroscopy within this spectral range. This device consists of two sets of parallel rod-shaped gold nanoantennas (NAs); the longer NAs produced an intense near-field amplification in the Amide I-II bands, while the shorter NAs were utilized to provide a sharp reflectivity edge at 1800–2200 cm−1 for EV mass-sensing. A clinically relevant subpopulation of EVs was targeted by conjugating NAs with an antibody specific to Epithelial Cell Adhesion Molecule (EpCAM). This methodology enabled the detection of variations in the quantity of EpCAM-presenting EVs and revealed changes in the Amide I-II lineshape. SignificanceThe presented results can positively impact the development of novel laboratory methods for the label-free characterization of EVs, based on the combination between mid-IR spectroscopy and plasmonics. Additionally, data obtained by using HCC and cirrhotic subjects as a model system, suggest that this approach could be adapted for monitoring these conditions.

Design of U-shaped peptides with long-lasting antifouling efficacy: Toward a feasible electrochemical aptasensor for robust detection in human serum

BackgroundDeveloping biosensors with antifouling properties is essential for accurately detecting low-concentration biomarkers in complex biological matrix, which is imperative for effective disease diagnosis and treatment. Herein, an antifouling electrochemical aptasensor qualifying for probing targets in human serum was explored based on newly-devised peptides that could form inverted U-shaped structures with long-term stability. ResultsThe inverted U-shaped peptides (U-Pep) with two terminals of thiol groups grafted onto the Au-modified electrode showcase superior antifouling properties in terms of high stability against enzymatic hydrolysis and long acting against biofouling in actual biofluids. The construction of the outlined antifouling electrochemical aptasensor just involved the fabrication of Au-deposited poly(3,4 ethylenedioxythiophene) (Au/PEDOT) modified electrode, followed by one-step co-incubation in the peptides and the aptamer probes with the Au/PEDOT electrode. Taking a typical biomarker of alpha-fetoprotein (AFP) for detection, this elegant antifouling aptasenor demonstrated a nice response for probing the target AFP with a low detection limit of 0.27 pg/mL and a wide linear scope of 1.0 pg/mL to 1.0 μg/mL, and furthermore qualified for assaying of AFP in human serum samples with satisfactory accuracy and feasibility. SignificanceThis engineering strategy of U-Pep with long-lasting antifouling efficacy opens a new horizon for high-performance antifouling biosensors suitable for detection in complex bifluids, and it could spark more inspiration for a follow-up exploration of other featured antifouling biomaterials.

Biofunctional photoelectrochemical/electrochemical immunosensor based on BiVO4/BiOI-MWCNTs and Au@PdPt for alpha-fetoprotein detection

A biofunctional immunosensor combining photoelectrochemical (PEC) and electrochemical (EC) was proposed for the quantitative detection of the liver cancer marker alpha-fetoprotein (AFP) in human blood. BiVO4/BiOI-MWCNTs photoactive materials were first prepared on conductive glass FTO, and the photoelectrode was functionalized by chitosan and glutaraldehyde. Then, the AFP capture antibody (Ab1) was successfully modified on the photoelectrode, and the label-free rapid detection of AFP antigen was achieved by PEC. In addition, Au@PdPt nanospheres were also used as a marker for binding to AFP detection antibody (Ab2). Due to the excellent catalytic properties of Au@PdPt in EC reaction, a signal increase in the EC response can be achieved when Ab2 binds to the AFP antigen, which ensures high sensitivity for the detection of AFP. The detection limits of PEC and EC are 0.050 pg/mL and 0.014 pg/mL, respectively. The sensor also possesses good specificity, stability and reproducibility, shows excellent performance in the detection of clinical samples and has good clinical applicability.

Assessment of Alpha Feto Protein in Patients with Hepatocellular Carcinoma Presenting to HCC Clinic During Era of COVID19 Pandemic

Abstract Background Hepatocellular carcinoma (HCC), a major health problem worldwide, is one of the most common primary neoplasms of the liver and one of the most common solid tumors in the world. More than 500,000 new cases were diagnosed each year. HCC accounts for between 85% and 90% of primary liver cancer. It is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Aim of the Work The aim of this study is to assess of alpha fetoprotein in patients who are diagnosed with hepatocellular carcinoma after COVID-19 infection. Patients and Methods This is cross Sectional Study on 60 Egyptian patients with HCC presenting to multidisciplinary clinic during era of Covid 19 pandemic divided into two subgroups: Group I: 30 patients with HCC and COVID 19 infection and group II: 30 patients with HCC who weren’t infected with COVID 19. Results In this study we found that there was insignificant difference between both studied groups as regards age and sex (p = 0.92 and p = 0.119, respectively). In this study we demonstrated that there was insignificant difference between both studied groups as regards etiology of HCC (p > 0.05). In this thesis we cleared that there was highly significant difference between both studied groups as regards Liver presentations (P < 0.001). In this thesis we found that there was significant difference between both studied groups as regards CBC (p < 0.05). In this study we demonstrated that there was significant difference between both studied groups as regards liver function tests (p < 0.05). Our results showed that that there was highly significant difference between both studied groups as regards AFP (p = 0.002). In study in our hands, we found that there was highly significant difference between both studied groups as regards tumor size and tumor stage (p < 0.001). In this study we found that there was highly significant difference between both studied groups as regards MELD score (p < 0.001). In this study we illustrated that Child Pugh class, MELD score, AFP and COVID-19 infection were the independent risk factors associated with poor survival among HCC patients Conclusion Our study concluded that tumor marker parameters, including AFP, can be used as Prognostic tools for HCC patients with СOVID-19. In which there were higher mortality rate among HCC with COVID-19 with higher levels of AFP.

Assessment of Galectin 3 as a New Biomarker of Liver Fibrosis in Chronic HCV Egyptian Patients and its Correlation to Transient Elastography, FIB-4 Index, and APRI Score

Abstract Background Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. Aim of the Work to evaluate serum Galectin-3 as a marker of liver fibrosis and correlate it to the stage of fibrosis assessed by FibroScan, FIB-4 index and APRI score Patients and Methods This was prospective study, was carried out on 30 patients with liver fibrosis/cirrhosis due to chronic HCV inthe Hepatic Virology Unit and the gastroenterology department of Ain Shams university hospitals and 30 health controls with normal, non fibrotic and non cirrhotic, liver, from January 2022 to June 2022 Results There were high significant difference between both groups as regard Serum level of Galectin-3 and APRI score. Conclusion Serum level of galectin-3 was highly expressed in chronic HCV Egyptain patients and positively correlated to FIB-4 index, APRI score and fibroscan.so the serum level of galectin-3 beside other modalities, lab investigations and clinical examination may guide us about the progression to fibrosis and cirrhosis in those patients. In these patients, if galectin-3 levels were found to be high, serum alpha-feto protein level and ultrasonographic examination could be repeated at more frequent intervals. This may also guide us in terms of the treatment plan. Measurement of galectin-3 in sera of large number of patients and follow up may pave the way to pick up early fibrosis and showed its prognostic effect.

Diagnostic Value of Plasma Methylated Septin 9 in Detection of Hepatocellular Carcinoma in Egyptian Patient with Post Hepatitis C Liver Cirrhosis in Comparison to Serum Level of Alphafeto Protein

Abstract Background Egypt has the highest hepatitis C virus (HCV) prevalence worldwide. Cirrhosis secondary to HCV is associated with the highest annual risk for developing hepatocellular carcinoma. The burden of HCC has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. HCC contributes to 14.8% of all cancer mortality in Egypt. Most HCCs (80%) arise in a cirrhotic liver, a situation where there has been longstanding hepatocyte damage and chronic inflammation leading to fibrosis. Aim of the Work This study aims to evaluate the diagnostic value of plasma mSEPT9 assay in detection of HCC in Egyptian patients with post hepatitis C liver cirrhosis in comparison to serum level of α-fetoprotein (AFP). Patients and Methods This is a prospective case-control study conducted at the Gastroenterology department in Ain Shams University Hospital. The study population consisted of 80 subjects, divided into three groups: 40 patients with hepatocellular carcinoma, 20 patients with liver cirrhosis, and 20 healthy subjects as controls with matched age and gender. Results The study found that hepatocellular carcinoma (HCC) was more frequent in male patients and that the age of HCC patients was statistically significantly higher than patients with cirrhosis and healthy controls. Patients with HCC and cirrhosis had a higher Child Pugh score than healthy controls. Portal hypertension and portal vein thrombosis were more frequent in HCC and cirrhosis patients than in the control group. Liver enzymes were higher in patients with HCC and cirrhosis compared to healthy controls, while hemoglobin and platelet levels were lower in patients with HCC. Hepatitis C antibody and PCR were positive in HCC and cirrhosis patient groups. AFP and Methylated Septin 9 levels were higher in patients with HCC and cirrhosis than in healthy controls, and AFP had better diagnostic accuracy than Methylated Septin 9. Both AFP and Methylated Septin 9 levels were positively correlated with age, Child Score, liver enzymes, and coagulation profile and negatively correlated with platelet count and hemoglobin level. AFP level was positively correlated with the number of focal lesions and liver size. Conclusion This study demonstrated that plasma Methylated Septin 9 can be a promising noninvasive and circulating epigenetic biomarker for HCC diagnosis at the individual level. However, our results showed that AFP was superior than Methylated Septin 9 in the detection of HCC, Methylated Septin 9 has higher Sensitivity. It was suggested that the combination of plasma mSEPT9 and AFP could enhance the sensitivity of Methylated Septin 9 or AFP alone in the diagnosis of HCC. Further comparative studies with larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events.

Role of Α-L-Fucosidase as a Diagnostic Marker versus Α-Fetoprotein in HCC Post Viral Cirrhotic Patients

Abstract Background Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third cause of cancer-related mortality world- wide. The incidence of HCC is on the increase, and it is a major threat to our modern life. Epidemiological studies have indicated that HCC are related to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Aim of the Work To evaluate the role of AFU as a diagnostic marker versus AFP in HCC post viral cirrhotic Egyptian patients. Patients and Methods This study had been carried out on 90 subjects, age range 21-75 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from January 2022 to June 2022. Results We found that serum levels of AFU were highest in patients of group A with HCC (129.867 ± 32.997 μl U/ml) compared to those with liver cirrhosis (33.433± 14.818 μl U/ml) with P value < 0.001 and the control groups (3.177 ± 1.199 μl U/ml) with P value < 0.001. Similarly alpha fetoprotein its serum levels were much higher in the HCC group (4688.223±11490.009 ng/ml) compared to the cirrhotic patients (4.407±3.107 ng/ml) with P value 0.02 Also, compared to healthy individuals (2.623±1.566 ng/ml) with p value 1.00. We found that there is No significant statistical correlation between serum AFP and AFU in our studied HCC and cirrhotic patients (R 0.332, P 0.073 for HCC and R 0.222, P 0.238 for cirrhotic). Regarding the negative correlation between serum AFU level and AFP level in order to predict the diagnostic value, sensitivity and specificity of both of them in term of tumor size, our study show that for AFU when the best cut off value was >52μl U/ml the sensitivity was 100% and specificity was 90% while for AFP when the best cut off value was > 10.5 ng/ml the sensitivity was 96.67% and specificity 96.67%. AFU is a promising serum tumor marker for HCC diagnosis and can be combined with AFP. Conclusion We concluded from this study that: Serum AFP was highly significant increase in HCC patients compared to cirrhotic and healthy controls, this is in agreement with many several reports that consider AFP in high serum levels as diagnostic for HCC combined with triphasic CT abdomen or dynamic MRI. Serum AFU levels were significantly higher in patients with HCC and mildly elevated in patients with liver cirrhosis compared to the control group. So it can be used as a tumor marker for HCC diagnosis. No correlation between AFU and laboratory data and child score. AFU was not influenced by clinical condition of the liver itself but with HCC. Around 40% of HCC patients have normal or low AFP level so AFU may be useful as a diagnostic marker in those patients. Serum AFP is the standard tumor marker used in clinical practice for diagnosis and surveillance of HCC in cirrhotic patients in spite of normal and low AFP HCC patients that may reach 40%. Sensitivity and specificity of AFU was nearly similar to sensitivity and specificity of AFP. Combined use of AFU with AFP or possibly other markers will improve the diagnostic field and can help in early detection of HCC in surveillance programms.

The Value of CEUS LI-RADS combined with AFP in early diagnosis of hepatocellular carcinoma in low- and high-risk patients.

We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP. We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP. Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014). The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.

Targeting AFP-RARβ complex formation: a potential strategy for treating AFP-positive hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is a glycoprotein primarily expressed during embryogenesis, with declining levels postnatally. Elevated AFP levels correlate with pathological conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent investigations underscore AFP's intracellular role in HCC progression, wherein it forms complexes with proteins like Phosphatase and tensin homolog (PTEN), Caspase 3 (CASP3), and Retinoic acid receptors and Retinoid X receptors (RAR/RXR). RAR and RXR regulate gene expression linked to cell death and tumorigenesis in normal physiology. AFP impedes RAR/RXR dimerization, nuclear translocation, and function, promoting gene expression favoring cancer progression in HCC that provoked us to target AFP as a drug candidate. Despite extensive studies, inhibitors targeting AFP to disrupt complex formation and activities remain scarce. In this study, employing protein-protein docking, amino acid residues involved in AFP-RARβ interaction were identified, guiding the definition of AFP's active site for potential inhibitor screening. Currently, kinase inhibitors play a significant role in cancer treatment and, the present study explores the potential of repurposing FDA-approved protein kinase inhibitors to target AFP. Molecular docking with kinase inhibitors revealed Lapatinib as a candidate drug of the AFP-RARβ complex. Molecular dynamics simulations and binding energy calculations, employing Mechanic/Poisson-Boltzmann Surface Area (MM-PBSA), confirmed Lapatinib's stability with AFP. The study suggests Lapatinib's potential in disrupting the AFP-RARβ complex, providing a promising avenue for treating molecularly stratified AFP-positive HCC or its early stages.

Progress and Outlook on Electrochemical Sensing of Lung Cancer Biomarkers.

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.

Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

Highly Elevated Alpha-fetoprotein Concentration in a Premature Infant

Alpha-1-fetoprotein (AFP) is a protein produced by the liver. Although its biological function is not fully understood, it is often used as a marker for cancer. High levels of AFP are also observed in premature infants. Reference ranges for AFP levels in premature infants are not specified. The authors present a case of a male newborn born at 25+5/7 weeks of gestational age. The boy underwent oncological diagnostics due to the detection, on the 24th day of life, of a liver lesion in an abdominal ultrasound examination, as well as significantly elevated AFP levels (&gt;430,000 ng/mL). With each passing day, the AFP level gradually decreased, and the suspicious lesion was not visualized on abdominal ultrasound or magnetic resonance imaging on the 59th day of life. Based on the conducted examinations, prematurity and its treatment were considered the cause of high AFP levels. The aim of the study was to present the diagnostic difficulties associated with the lack of AFP norms for premature infants.

TLK2 promotes progression of hepatocellular carcinoma through Wnt/β-catenin signaling.

Hepatocellular carcinoma is a widespread cancer worldwide, ranking as the fifth most frequent cancer and the fourth leading cause of cancer-related deaths. According to comprehensive research, TLK2, a phosphorylated kinase, has been discovered to play a crucial role in promoting tumor development. However, the prognostic significance and influence of TLK2 on hepatocellular carcinoma tumor cells and the immune microenvironment remain unexplored, warranting further investigation. The aim of this study was to investigate the role of TLK2 in promoting the development of hepatocellular carcinoma. The present study utilized The Cancer Genome Atlas (TCGA) database and other databases as training sets to examine the expression of TLK2 and its prognostic significance. The findings were subsequently validated through cell proliferation assays and cell colony assays. Gene set enrichment analysis (GSEA) was employed to investigate the tumor-related biological processes associated with TLK2 in hepatocellular carcinoma, while the relationship between TLK2 expression and Wnt/β-catenin signaling pathway was analyzed via TCGA dataset analysis. Western blotting and immunofluorescence assays were used to confirm the experimental results. TLK2 showed higher expression levels in tumor tissues than in normal tissues. Alpha fetoprotein (AFP), T stage, pathological stage, and histological grade were significantly associated with TLK2 expression. High TLK2 expression correlated with worse overall survival (OS) [hazard ratio (HR) =1.62, 95% confidence interval (CI): 1.14-2.29, P=0.007], progression-free survival (PFS) (HR =1.88, 95% CI: 1.40-2.52, P<0.001) and disease specific survival (DSS) (HR =1.86, 95% CI: 1.18-2.93, P=0.007) in the training and validation sets. Both univariate and multivariate analyses showed that TLK2 was an independent prognostic factor. GSEA showed that TLK2 was significantly enriched in tumor-related biological processes. TLK2 induced the activation of β-catenin signaling, resulting in sustained tumor growth. Methyl thiazolyl tetrazolium (MTT) and colony formation assays demonstrated that TLK2 could promote hepatocellular carcinoma progression. Furthermore, TLK2 showed a significant association with β-catenin in the Wnt pathway. TLK2 represents an independent prognostic factor in hepatocellular carcinoma and can promote cancer progression via the β-catenin signaling pathway.

The study of Alpha-Fetoprotein (AFP) levels before and after treatment of Hepatitis C Virus in Egyptian patients

The study of Alpha-Fetoprotein (AFP) levels before and after treatment of Hepatitis C Virus in Egyptian patients

Clinical features and prognostic factors of patients with inoperable hepatocellular carcinoma treated with chemotherapy: a population-based study.

In inoperable hepatocellular carcinoma (HCC), chemotherapy is a common treatment strategy. However, there is a lack of reliable methods to predict the prognosis of patients with inoperable HCC after chemotherapy. Therefore, the aim of this study was to identify the clinical characteristics of patients with inoperable HCC and to establish and validate nomogram models for predicting the survival outcomes in this patient group following chemotherapy. The data of patients diagnosed with HCC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Logistic regression analyses were used to identify potential factors for inoperability in patients with HCC. Kaplan-Meier analyses were applied to evaluate the impact of chemotherapy on prognosis. Additionally, Cox regression analyses were performed to identify the potential risk factors associated with overall survival (OS) and cancer-specific survival (CSS) in patients with inoperable HCC treated with chemotherapy. Finally, we constructed prognostic nomograms for predicting the 1- and 3-year survival probabilities. A total of 3,519 operable patients with HCC and 4,656 patients with inoperable HCC were ultimately included in this study. Logistic regression analyses revealed a significant association between patient age, gender, race, tumor, node, metastasis (TNM) stage, tumor size, pretreatment alpha fetoprotein (AFP) levels, and marital status with inoperability. Moreover, Kaplan-Meier analyses revealed a significant improvement in both OS and CSS with the administration of chemotherapy. Moreover, 1,456 patients with inoperable HCC were enrolled in the training group and 631 patients with inoperable HCC were enrolled in the validation group to develop and validate the prognostic models. Cox regression models indicated that TNM stage, tumor size, and pretreatment AFP were independent risk factors for predicting OS and CSS in patients with inoperable HCC receiving chemotherapy. These factors were subsequently integrated into the predictive nomograms. We preliminarily developed survival models with strong predictive capabilities for estimating survival probabilities in patients with HCC following chemotherapy. These models hold potential for clinical application and warrant further exploration through additional studies.

A Label-Free Photoelectrochemical Biosensor Based on ZnO/Cs3MnBr5 Heterogeneous Films for Alpha-Fetoprotein Detection.

Highly sensitive and specific biomarker detection is of outstanding importance for the diagnosis and treatment of cancers. Herein, we developed robust photoelectrochemical (PEC) biosensors with low background noise and high sensitivity based on a heterojunction, which can improve semiconductor photoelectric properties by limiting the recombination of photogenerated electron-hole pairs and successfully widening the range of light absorption. Alpha-fetoprotein (AFP) was used as a target model to examine the analytical performances of the designed PEC biosensors. ZnO/Cs3MnBr5 heterogeneous film with a uniform porous structure and large surface area enhanced electron transfer and biomolecule immobilization, and significantly increased the photocurrent response. Under the optimal conditions, the designed PEC biosensor exhibited a linear detection range of 0.01-500 ng/mL and a detection limit of 12 pg/mL. In addition, this PEC biosensor performed well when testing human serum samples and exhibited good repeatability, stability over time, and specificity, showing enormous potential for the detection of cancer markers in future biological and clinical research.

Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer.

The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear. To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer. Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures. One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group (P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group (P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant (P < 0.05). And there were no statistical differences in complications between the two groups (P > 0.05). TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Serum tumor marker and CT body composition scoring system predicts outcomes in colorectal cancer surgical patients.

To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.

The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

Nanobody-enhanced split-luciferase technology for innovative detection of the liver cancer biomarker alpha-fetoprotein

Liver cancer is one of the most common cancers and the third leading cause of cancer deaths worldwide. Diagnosis and screening for liver cancer rely on the alpha-fetoprotein (AFP) biomarker. This study aimed to pioneer a novel assay for AFP detection utilizing a tri-part split-luciferase system in conjunction with nanobodies targeting AFP. The strategy involved fusing anti-AFP nanobodies P5 and P15 to the split-nanoluciferase components β9 and β10, respectively. Upon binding to AFP and in the presence of the third nanoluciferase component Δ11S, the proximity-induced reassembly of split-nanoluciferase components triggers luciferase activation and luminescence emission. Following expression in a bacterial system, purification, and assay implementation, the developed assay exhibited high sensitivity in detecting AFP within a linear range of 1–20 ng/ml, with a Limit of Detection (LOD) of 0.5 ng/ml. The assay results were in line with those obtained from ELISA, indicating its efficiency. This study highlights the specificity of the homogenous assay developed with nanobodies for AFP, offering a reliable and user-friendly test for AFP detection.