Performance of Intracystic Glucose Measurement for the Characterization of Pancreatic Cystic Lesions.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is essential for the classification of pancreatic cystic lesions (PCLs). Recently, intracystic glucose has been suggested as an alternative to carcinoembryonic antigen (CEA) level as a predictor of mucinous cystic lesions (M-PCLs). This study aims to evaluate the diagnostic performance of intra-cystic glucose in distinguishing between M-PCLs and non M-PCLs (NM-PCLs) and to analyze the possibility of on-site glucose measurement with a standard glucometer. METHODS: Patients with PCLs submitted to EUS-FNA with simultaneous intracystic glucose measurement between 2017 and 2022 were included. The diagnostic performance of glucose versus CEA for the differentiation between M-PCLs and NM-PCLs was compared to a final diagnosis based on the analysis of surgical specimen, intracystic biopsy or, if this data was unavailable, multidisciplinary evaluation. A cut-off of <50 mg/dL was used for the diagnosis of MCLs. Additionally, the agreement between on-site glucose determination with a standard glucometer and laboratory glucose measurement was assessed. RESULTS: Mucinous lesions accounted for 56% of all PCLs. The median values of glucose and CEA for M-PCLs were 18 mg/dL and 286 ng/mL, respectively. Intracystic glucose had a sensitivity and specificity of 93.2% and 76.5%, respectively, for the diagnosis of MCLs (versus 55.6% and 87.5%, respectively, for CEA). The area under the curve was 0.870 for on-site glucose (versus 0.806 for CEA). An excellent correlation was observed between on-site and laboratory glucose measurement (ρ=0.919). CONCLUSIONS: The measurement of intracystic glucose showed superior performance compared with CEA in distinguishing between M-PCLs and NM-PCLs, with excellent correlation between on-site and conventional lab glucose measurement. Thus, on-site intracystic glucose appears to be an excellent biomarker for the characterization of PCLs due to its low cost, high availability, and the need for a minimal cyst fluid volume for its determination.

Elevated postoperative carcinoembryonic antigen guides adjuvant chemotherapy for stage II colon cancer: a multicentre cohort retrospective study.

Most clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients' recurrence free survival (RFS). The Kaplan-Meier method was used to create the patients' RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0-88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5-86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1-93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22-2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5-96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8-71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51-49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer.

Realizing the label-free sensitive detection of carcinoembryogenic antigen (CEA) in blood serum via a MNC-decorated flexible immunosensor.

A label-free electrochemical immunosensor utilising nitrogen-rich mesoporous carbon (MNC) as the substrate material was developed for the sensitive quantification of carcinoembryonic antigen (CEA). The synergic interactions between MNC and AbCEA also eliminated the need for coupling agents such as EDC/NHS. The novel immunosensor demonstrated a wide detection range from 500 fM (9.04 pg mL-1) to 50 nM (1 µg mL-1) and a low detection limit (LOD) of 500 fM. Moreover, the immunosensor showed sensitivities of 12.27 mA nM-1 cm-2 and 0.066 mA nM-1 cm-2 for detecting CEA in the linear ranges 10 pM to 1 nM and 2 nM to 50 nM, respectively, while maintaining long-term storage stability of 6 weeks. Analysis of real serum sample analysis yielded highly accurate results with recovery rates ranging from 99.3% to 103.7%. Furthermore, the developed paper-based screen-printed electrode exhibited a similar detection range, suggesting its potential for use in point-of-care detection devices in future applications.

Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review.

OBJECTIVE: Elevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts. DESIGN: 1169 pancreatic cysts (1999-2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstrated KRAS, GNAS, or RNF43 mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts. RESULTS: Median CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p<0.001). Receiver operating characteristic curve analysis demonstrated an optimal CEA cut-off of 20 ng/mL (area under the curve: 80%), though the specificity was lower than desired (sensitivity 89%, specificity 64%). At the previously established threshold of 192 ng/mL, sensitivity and specificity were 56% and 78%, respectively. To achieve a specificity of 85% as originally reported, a CEA threshold of 250 ng/mL was needed; the 13 false positive cases at this threshold included 4 benign simple cysts, 2 squamoid cysts, 1 serous cystadenoma, 1 lymphoepithelial cyst and 5 more uncommon entities. All results remained similar within the total cohort after including additional cases with KRAS/GNAS/RNF43 mutations only. CONCLUSION: Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered.

Diagnosis and treatment of hepatic cysts. Usefulness of intracystic tumor markers (CEA and CA 19.9.).

INTRODUCTION: To decide treatment of hepatic cysts diagnosis between simple hepatic cyst (SHC) and cystic mucinous neoplasm (CMN). Radiological features are not patognomonic. Some studies have suggested the utility of intracystic tumor markers. METHODS: Retrospective analysis of our prospective database including patients treated due to symptomatic SHC from 2003 to 2021. The aim of the study was to evaluate the results of treatment of symptomatic SHC and the usefulness of the determination of intracystic "carcinoembryonic antigen" (CEA) and "carbohydrate antigen" CA 19.9. RESULTS: 50 patients diagnosed and treated for symptomatic SHC were included. In 15 patients the first treatment was percutaneous drainage. In 35 patients the first treatment was laparoscopic fenestration. Four patients were diagnosed of premalignant or malignant liver cystic lesions (MCN, IPMN, lymphoma B); three of them required surgery after initial fenestration and pathological diagnosis. Median CEA and CA 19-9 were 196 µg/L and 227.321 U/mL respectively. Patients with malignant or premalignant pathology did not have higher levels of intracystic tumor markers. Positive predictive value was 0% for both markers, and negative predictive value was 89% and 91% respectively. CONCLUSION: Values of intracystic tumor markers CEA and CA 19-9 do not allow distinguishing simple cysts from cystic liver neoplasms. The most effective treatment for symptomatic simple liver cysts is surgical fenestration. The pathological analysis of the wall of the cysts enables the correct diagnosis, allowing to indicate a surgical reintervention in cases of hepatic cyst neoplasia.

Multiplexed immunosensing of cancer biomarkers on a split-float-gate graphene transistor microfluidic biochip.

This work reports the development of a novel microfluidic biosensor using a graphene field-effect transistor (GFET) design for the parallel label-free analysis of multiple biomarkers. Overcoming the persistent challenge of constructing µm2-sized FET sensitive interfaces that incorporate multiple receptors, we implement a split-float-gate structure that enables the manipulation of multiplexed biochemical functionalization using microfluidic channels. Immunoaffinity biosensing experiments are conducted using the mixture samples containing three liver cancer biomarkers, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and parathyroid hormone (PTH). The results demonstrate the capability of our label-free biochip to quantitatively detect multiple target biomarkers simultaneously by observing the kinetics in 10 minutes, with the detection limit levels in the nanomolar range. This microfluidic biosensor provides a valuable analytical tool for rapid multi-target biosensing, which can be potentially utilized for domiciliary tests of cancer screening and prognosis, obviating the need for sophisticated instruments and professional operations in hospitals.

2D Z-scheme ZnIn2S4/g-C3N4 heterojunction based on photoelectrochemical immunosensor with enhanced carrier separation for sensitive detection of CEA.

Semiconducting materials based on photoelectrochemical (PEC) sensors have been widely utilized for detection. Meanwhile, the sensitivity of the PEC sensor was limited by low-efficiency carrier separation. Thus, a novel sandwich-type PEC bioimmunosensing based on 2D Z-scheme ZnIn2S4/g-C3N4 heterojunction as a photosensitive material and BiVO4 as a photoquencher was designed for the sensitive detection of carcinoembryonic antigen (CEA). Firstly, the 2D ZnIn2S4/g-C3N4 structure provided a multitude of activated sites which facilitated the loading of the capture antibody (Ab1). Secondly, the Z-scheme heterojunction had a high redox capacity while promoting the rapid separation and migration of photogenerated electron-hole pairs (e-/h+). Thus it was able to consume more electron donors to a certain extent, resulting in a higher initial photocurrent. In addition, BiVO4 with large spatial potential resistance was introduced for the first time to realize signal amplification. BiVO4 could not only compete with substrate materials for electron donors, but also effectively prevent electron donors from contacting the substrate, further reducing the photocurrent signal. Under optimized conditions, the sensor had a favorable detection range (0.0001-100 ng/mL) to CEA and a low detection limit of 0.03 pg/mL. With high specificity, excellent stability, and remarkable reproducibility, this sensor provided a new perspective for constructing accurate and convenient PEC immunosensor for bioanalysis and early disease diagnosisdisease diagnosis.

Development and validation of a machine learning model for differential diagnosis of malignant pleural effusion using routine laboratory data.

BACKGROUND: The differential diagnosis of malignant pleural effusion (MPE) and benign pleural effusion (BPE) presents a clinical challenge. In recent years, the use of artificial intelligence (AI) machine learning models for disease diagnosis has increased. OBJECTIVE: This study aimed to develop and validate a diagnostic model for early differentiation between MPE and BPE based on routine laboratory data. DESIGN: This was a retrospective observational cohort study. METHODS: A total of 2352 newly diagnosed patients with pleural effusion (PE), between January 2008 and March 2021, were eventually enrolled. Among them, 1435, 466, and 451 participants were randomly assigned to the training, validation, and testing cohorts in a ratio of 3:1:1. Clinical parameters, including age, sex, and laboratory parameters of PE patients, were abstracted for analysis. Based on 81 candidate laboratory variables, five machine learning models, namely extreme gradient boosting (XGBoost) model, logistic regression (LR) model, random forest (RF) model, support vector machine (SVM) model, and multilayer perceptron (MLP) model were developed. Their respective diagnostic performances for MPE were evaluated by receiver operating characteristic (ROC) curves. RESULTS: Among the five models, the XGBoost model exhibited the best diagnostic performance for MPE (area under the curve (AUC): 0.903, 0.918, and 0.886 in the training, validation, and testing cohorts, respectively). Additionally, the XGBoost model outperformed carcinoembryonic antigen (CEA) levels in pleural fluid (PF), serum, and the PF/serum ratio (AUC: 0.726, 0.699, and 0.692 in the training cohort; 0.763, 0.695, and 0.731 in the validation cohort; and 0.722, 0.729, and 0.693 in the testing cohort, respectively). Furthermore, compared with CEA, the XGBoost model demonstrated greater diagnostic power and sensitivity in diagnosing lung cancer-induced MPE. CONCLUSION: The development of a machine learning model utilizing routine laboratory biomarkers significantly enhances the diagnostic capability for distinguishing between MPE and BPE. The XGBoost model emerges as a valuable tool for the diagnosis of MPE.

Isoniazide modified Ag nanoparticles triggered photothermal immunoassay for carcinoembryonic antigen detection.

As the most well-known analytical tool, the thermometer has been extended to the field of biological analysis based on the photothermal effect. Herein, isoniazide modified Ag nanoparticles were prepared as nanolabels to build an immunoassay. The nanoparticles were characterized by transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray powder diffraction (XRD), and Fourier transform infrared (FT-IR). When the target protein was present, the sandwich immunoassay was developed and the photothermal reaction was triggered by isoniazide modified Ag nanoparticles. As a reducing agent, isoniazide is used to transform phosphomolybdic acid hydrate into molybdenum blue solution. And molybdenum blue had good photothermal stability and high photothermal conversion efficiency. The temperature variation of molybdenum blue solution showed a positive correlation with the concentration of carcinoembryonic antigen (CEA). Thus, the target protein of CEA was quantitative detection by thermometer. The linear response range is 0.1 ng mL-1 to 40 ng mL-1, and the detection limit is 0.08 ng mL-1. Moreover, the proposed protocol had satisfactory selectivity, accuracy, and reproducibility.

Cation Exchange Reaction-Mediated Photothermal and Polarity-Switchable Photoelectrochemical Dual-Readout Biosensor.

Cation exchange (CE) is a burgeoning method for controlled crystal synthesis; however, its applications in bioanalysis are still in their infancy. Herein, we explored the transformation of ZnIn2S4 in properties after the CE reaction with Cu2+ ions; furthermore, the discrepancy was employed to design a dual-readout detection system of photothermal and polarity-switchable photoelectrochemical (PEC) immunoassays to realize reliable detection of carcinoembryonic antigen (CEA). In the presence of CEA, the CuO nanoparticles (CuO NPs) employed as dual-signal response probes would bond to the microplates and be acidolyzed by HCl to release Cu2+, which could replace Zn2+ and In3+ via the CE reaction. After the CE reaction is completed, the photocurrent would switch from a weak anodic photocurrent to a cathode one by using a 635 nm laser as a signal amplifier, while the photothermal signal would be enhanced with 808 nm laser illumination. On the basis of the polarity-switchable PEC strategy, CEA could be accurately detected from 0.1 to 50 ng mL-1 with a limit of detection (LOD) of 48 pg mL-1 (S/N = 3). Moreover, the photothermal assay for CEA detection possesses a linear range from 0.5 to 100 ng mL-1 with a LOD of 0.21 ng mL-1. In addition, the designed sensing platform only relies on devices with portability that are permitted for point-of-care detection.

Colorimetric immunoassay of carcinoembryonic antigen based on the glucose oxidase/MnO2 nanosheet cascade reaction with self-supplying oxygen.

The detection of carcinoembryonic antigen (CEA) has profound implications in cancer diagnostics and therapeutic monitoring. In this work, we developed a colorimetric immunoassay for the detection of CEA. This assay involves the utilization of zinc(II)-based coordination polymers (ZnCPs) as a host for integrating glucose oxidase (GOx) and anti-carcinoembryonic antigen antibody (anti-CEA), which results in the formation of a detection antibody (anti-CEA/GOx@ZnCPs). The adaptable inclusion properties of ZnCPs enable the preservation of the original catalytic behavior of GOx and antigen capture ability of anti-CEA. Consequently, the anti-CEA/GOx@ZnCPs can act as a detection antibody to facilitate the development of an immunoassay. The combination of anti-CEA/GOx@ZnCPs in the immunoassay triggers a cascade reaction involving GOx and MnO2 nanosheets, leading to the generation of an amplified colorimetric signal through self-supplying oxygen. This colorimetric immunoassay exhibits a linear response ranging from 2 to 180 ng mL-1 CEA and has a detection limit of 50 pg mL-1. The practicality of this colorimetric immunoassay in biological matrices was demonstrated by the successful determination of CEA in serum samples with good recovery and precision. We believe that this study will pave the way to rationally design multifunctional CP-based composites for a wide range of applications in bioanalysis.

Application of Ag nanoparticles decorated on graphene nanosheets for electrochemical sensing of CEA as an important cancer biomarker.

In this research, a novel biosensing platform is described based on graphene nano-sheets decorated with Ag nano-particles (GNSs@Ag NPs). The designed electrochemical aptasensor was employed to determine carcinoembryonic antigen (CEA), an important cancer biomarker. Inherently, aptasensing interfaces provide high sensitivity for CEA tumor marker because of the high specific surface area and excellent conductivity of the prepared GNSs@Ag NPs composite. The established assay demonstrated a wide linear range from 0.001 pg/mL to 10 pg/mL with a correlation coefficient of 0.9958 and low detection limit (DL) of 0.5 fg/mL based on S/N = 3 protocol. The derived biosensor illustrated acceptable selectivity towards common interfering species including HER2, VEGF, IgG, MUC1 and CFP10. In addition, the aptsensor showed good reproducibility and fast response time. The applicability of the suggested strategy in human serum samples was also examined and compared to the commercial enzyme-linked immunosorbent assay (ELISA). Based on the experimental data, it was found that the discussed sensing platform can be exerted in the monitoring of CEA in different cancers for early diagnosis.

Achieving enhanced sensitivity and accuracy in carcinoembryonic antigen (CEA) detection as an indicator of cancer monitoring using thionine/chitosan/graphene oxide nanocomposite-modified electrochemical immunosensor.

The current study has focused on electrochemical immunosensing of carcinoembryonic antigen (CEA) employing an immobilized antibody on a thionine, chitosan, or graphene oxide nanocomposite modified glassy carbon electrode (anti-CEA/THi-CS-GO/GCE) as an indicator of cancer monitoring. THi-CS-GO nanocomposites were made using ultrasonication, and analyses of their morphology and crystal structure using SEM, FTIR, and XRD showed that thionine and chitosan molecules were intercalated with stacking interactions with both the top and bottom of GO nanosheets. Electrochemical experiments revealed anti-CEA, THi-CS-GO/GCE to have exceptional sensitivity and selectivity towards CEA compounds. The detection limit value was established to be 0.8 pg/mL when it was discovered that variations in the decrease peak current were directly proportional to the logarithm concentration of CEA over a wide range from 10-3 to 104 ng/mL. Results of testing the immunosensor's application capability for detecting CEA in a sample of human serum show that ELISA and DPV results are very congruent. The produced immunosensor demonstrated adequate immunosensor precision in determining CEA in prepared genuine samples of human serum and clinical applications.

Development of a high-performance label-free electrochemical immunosensor for early cancer diagnosis using anti-CEA/Ag-MOF/GO/GCE nanocomposite.

In order to detect carcinoembryonic antigen (CEA) as a tumor marker in lung cancer for early cancer diagnosis, this study aimed to develop a label-free electrochemical immunosensor based on the immobilization of an Anti-CEA antibody on a metal-organic framework (MOF)-graphene oxide nanocomposite modified glassy carbon electrode (Anti-CEA/Ag-MOF/GO/GCE). Ag-MOF/GO nanocomposite was prepared on the GCE surface using the ultrasonic irradiation method, and Anti-CEA antibody was subsequently immobilized on the surface. Analysis of the crystal structure and morphology of the modified electrode using FE-SEM and XRD revealed that the correct combination of GO nanosheets and Ag-MOF nanoparticles produced a high surface area to trap the antibodies. Electrochemical tests utilizing the CV and DPV methods revealed that the immunosensor's sensitivity, stability, and selectivity were improved by Anti-CEA/Ag-MOF/GO/GCE. Results showed that, with a detection limit of 0.005 ng/mL, the change in the reduction peak current was inversely correlated with the logarithm concentration of CEA in the range of 10-3 to 5000 ng/mL. The suggested CEA immunosensor's applicability in a human serum sample was investigated, and findings of analytical studies via standard addition technique for both ELISA and DPV assays revealed that significant agreement existed between the outcomes of the two assays. Additionally, the recoveries ranged from 99.00% to 99.25%, and all relative standard deviations (RSDs) for the sample detections were below 5.01%, indicating satisfactory accuracy in results measured with the proposed CEA immunosensor, indicating that the prepared CEA immunosensor in this study can be used in clinical applications and human fluids.

A biosensor based on graphene oxide nanocomposite for determination of carcinoembryonic antigen in colorectal cancer biomarker.

Colorectal cancer is still a major global health concern, and early detection and accurate biomarker analyses are critical to its successful management. This paper describes the design and testing of a new biosensor based on a graphene oxide (GO) nanocomposite for the exact measurement of carcinoembryonic antigen (CEA), a well-known biomarker for colorectal cancer. The current study attempted to create a highly sensitive immunosensor for sensitive measurement of CEA based on a polypropylene-imine-dendrimer (PPI) and GO nanocomposite on GCE (PPI/GO/GCE). The PPI/GO nanocomposite served as an appropriate biocompatible nanostructure with a large surface area for immobilizing carcinoembryonic antigen (anti-CEA) and bovine serum albumin (BSA) molecules (BSA/anti-CEA/PPI/GO/GCE), thereby promoting the selectivity of electrochemical immunosensors, according to structural and electrochemical studies. Results showed that the BSA/anti-CEA/PPI/GO/GCE as a selective, sensitive, and stable immunosensor revealed a wide linear response from 0.001 to 2000 ng/mL, and a limit of detection of 0.3 pg/mL, which indicated comparable or better performance towards the CEA immunosensors in recent reports in the literature. This was due to the synergetic effect of the GO nanosheets and PPI with porous structure and more conductivity. Analytical results showed values of RSD (4.49%-5.04%) and recovery (90.00%-99.98%) are suitable for effective and accurate practical assessments in CEA in clinical samples. The capacity of the BSA/anti-CEA/PPI/GO/GCE to determine CEA in human blood was studied.

Impedimetric aptasensor based on MOF based composite for measuring of carcinoembryonic antigen as a tumor biomarker.

In this research, gold nanoparticle (GNPs)-modified metal-organic framework/reduced graphene oxide (MOF(801)/rGO) hybrid was employed to design a new aptasensor for carcinoembryonic antigen (CEA) quantification in biological sample. The sensing ability of the electrode for CEA biomarker was examined with electrochemical impedance spectroscopy (EIS) and cyclic voltammetry procedures. Besides, CEA was electrochemically quantified by the EIS method. With respect to the high surface-to-volume ratio of MOF(801) and the good electron transfer ability of rGO, the proposed sensor displayed notable sensitivity and reliability in the CEA analysis. The derived electrode showed an appreciable detection limit of 0.8 pg L-1 using EIS protocol. In addition, the present aptasensor revealed diverse advantages including anti-interference property, wide linear range (0.0025-0.25 ng L-1), convenience and high efficiency toward CEA quantification. More importantly, the performance of the suggested assay remains unchanged in analysis of CEA in body fluids. The established assay demonstrates that the suggested biosensor is a promising device in clinical diagnosis.

Enzyme-catalyzed high-performing reaction with in-situ amplified photocurrent on carbon-functionalized inorganic photoanode for immunosensing.

An enzyme-catalyzed high-performing reaction with in-situ amplified photocurrent was innovatively designed for the quantitative screening of carcinoembryonic antigen (CEA) in biological fluids by coupling with carbon-functionalized inorganic photoanode. A split-type photoelectrochemical (PEC) immunoassay was initially executed with horseradish peroxidase (HRP)-labeled secondary antibody on the capture antibody-coated microtiter. Then, the photocurrent of carbon-functionalized inorganic photoanode were improved through enzymatic insoluble product. Experimental results revealed that introduction of the outer carbon layer on the inorganic photoactive materials caused the amplifying photocurrent because of the improving light harvesting and separation of photo-generated e-/h+ pairs. Under optimum conditions, the split-type photoelectrochemical immunosensing platform displayed good photocurrent responses within the dynamic range of 0.01 - 80 ng mL-1 CEA, and allowed the detection of CEA as low as a concentration of 3.6 pg mL-1 at the 3Sblank level. The strong attachment of antibodies onto nano label and high-performing photoanode resulted in a good repeatability and intermediate precision down to 9.83%. No significant differences at the 0.05 significance level were encountered in the analysis of six human serum specimens between the developed PEC immunoassay and the commercially available CEA ELISA kits.

Electrochemiluminescence imaging of a membrane carcinoembryonic antigen at single tissue sections.

Histopathological molecular testing of tissue sections is an essential step in tumor diagnosis; however, the commonly used immunohistochemical methods have problems such as low specificity and the subjective bias of the observer. Here, we report an electrochemiluminescence (ECL) imaging method to detect a membrane carcinoembryonic antigen (CEA) at the single tissue sections of cancer patients. By permeabilizing the tissue attached to a glassy carbon electrode, Ru(bpy)32+ tagged at the membrane CEA of the tissue could electrochemically react with TPrA in solution to emit ECL that has near-zero background and an extremely high signal-to-background ratio. Using the established ECL method, the expression differences and distribution characteristics of the CEA protein in the carcinoma and paracancerous tissues of pancreatic ductal carcinoma (PDAC) and lung adenocarcinoma (LUAD) patients are investigated. The images reveal that CEA proteins are mostly distributed in the acini and surrounding areas both in PDAC and LUAD tissues. Therefore, the presented approach could be able to provide a new molecular recognition method for the diagnosis of adenocarcinoma and other tumors.

Predictive ability of pancreatic cyst fluid biomarkers: A systematic review and meta-analysis.

BACKGROUND: Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts. METHODS: We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC. RESULTS: Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts. CONCLUSIONS: Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.

Electrochemiluminescence Immunosensors Based on ECL-RET Triggering between Mn SANE/PEI-Luminol and PtCu/h-MPF for Ultrasensitive Detection of CEA.

In this paper, a novel donor-acceptor pair was creatively proposed based on the principle of electrochemiluminescence resonance energy transfer (ECL-RET): luminol immobilized on polyethyleneimine (PEI)-functionalized manganese-based single-atom nanozymes (Mn SANE/PEI-luminol, donor) and a PtCu-grafted hollow metal polydopamine framework (PtCu/h-MPF, acceptor). A quenched ECL immunosensor was constructed for the ultrasensitive analysis of carcinoembryonic antigen (CEA). Mn SANE, as an efficient novel coreaction accelerator with the outstanding performance of significantly activating H2O2 to produce large amounts of ROS, was further modified by the coreactant PEI, which efficiently immobilized luminol to form a self-enhanced emitter. As a result, the electron transport distance was effectively shortened, the energy loss was reduced, and luminol achieved a high ECL efficiency. More importantly, PtCu-grafted h-MPF (PtCu/h-MPF) was proposed as a novel quencher. The UV-vis spectra of PtCu/h-MPF partially overlap with the ECL spectra of Mn SANE/PEI-luminol, which can effectively trigger the ECL-RET behavior between the donor and the acceptor. The multiple quenching effect on Mn SANE/PEI-luminol was achieved, which significantly improved the sensitivity of the immunosensor. The prepared immunosensor exhibited good linearity in the concentration range of 10-5 to 80 ng/mL. The results indicate that this work provides a new method for the early detection of CEA in clinical diagnosis.