Detection Of CEA Research Articles

CEA和D-二聚体检测对胃癌诊断及手术后患者预后的评估价值

CEA和D-二聚体检测对胃癌诊断及手术后患者预后的评估价值

The DNA controllable peroxidase mimetic activity of MoS2 nanosheets for constructing a robust colorimetric biosensor.

The low activity of nanozymes, which work as an alternative to natural enzymes, limits their applications in the fabrication of biosensors, drawing increasing attention aimed at improving their catalytic capacity. In this work, the peroxidase-like activity of MoS2 nanosheets (NSs) was dramatically enhanced through DNA modification, and was 4.3-times higher than that of bare MoS2 NSs. Such an enhancement of catalytic activity was mainly ascribed to the increased affinity of the DNA/MoS2 NSs toward the substrate, TMB, further accelerating electron transfer from TMB to H2O2. On the basis of DNA-tuned MoS2 NS nanozyme activity, a colorimetric sensing platform was developed for the facile detection of carcinoembryonic antigen (CEA) in a sensitive manner. Interestingly, a convenient, affordable, and instrument-free portable test kit was fabricated to visually monitor CEA via rooting the aptamer/MoS2 NS system into an agarose hydrogel. Importantly, our work illuminates the feasibility of using DNA to enhance the catalysis of nanozymes and their application potential in the label-free, portable, and visual detection of aptamer-targeted biomolecules.

A perylenetetracarboxylic dianhydride and aniline-assembled supramolecular nanomaterial with multi-color electrochemiluminescence for a highly sensitive label-free immunoassay.

Most electrochemiluminescence (ECL) studies focus on the single emission of luminophores, which severely limits the development of the multi-color ECL fundamental theory and applications. Herein, we prepared a multi-color ECL supramolecular nanomaterial self-assembled by 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) and aniline (An) through hydrogen bonding. This PTCDA-An supramolecular nanomaterial simultaneously produced multi-color emissions peaking at 486, 692 and 760 nm with K2S2O8 as a coreactant. These multi-color emissions were assigned to the excited PTCDA monomer (486 nm), H-dimer (692 nm) and J-dimer (760 nm). The simultaneously increased dual-color ECL intensity significantly enhanced the total ECL intensity of PTCDA-An. Furthermore, this highly efficient ECL nanomaterial was used as an ECL platform to construct a label-free immunosensor for tumor marker carcinoembryonic antigen (CEA) detection. The total ECL intensity of the immunosensor sensitively decreased due to the simultaneously decreased ECL of multiple emissions. Also, this immunosensor exhibited a wide linear range from 1 pg mL-1 to 10 μg mL-1 with a low detection limit of 0.23 pg mL-1. The multi-color ECL from the same luminophore PTCDA in this work also provides a new perspective for multi-color ECL biomaterial design.

A Colorimetric Immunoassay Based on Coordination Polymer Composite for the Detection of Carcinoembryonic Antigen.

Coordination polymers (CPs) as fascinating materials have been explored in a number of fields due to their diverse properties. In this work, we demonstrate the feasibility of CPs in the facile fabrication of multifunctional composites for establishing an immunoassay. To this end, a zinc(II)-based CP (ZnCP) with adenine as a bridge ligand was employed to integrate with alkaline phosphatase (ALP) and anticarcinoembryonic antigen (anti-CEA) antibody, which produces ALP/anti-CEA@ZnCPs. Benefiting from the adaptive inclusion property of ZnCPs, the integrated ALP and anti-CEA can maintain their original catalytic activity and capture ability to target antigen, respectively. This allows the ALP/anti-CEA@ZnCPs to be a detection antibody for performing an immunoassay. Meanwhile, ZnCP as a host can effectively protect the loaded ALP and anti-CEA against harsh environments. On this basis, by using iron(II)-phenanthroline complex as a signal amplifier, a colorimetric immunoassay for CEA detection was developed, and a low detection limit of 21.1 pg/mL has been achieved. This immunoassay was successfully applied to determine CEA levels in serum samples with good recovery and precision. We believe that this study can not only provide a new method for CEA detection but also open up a new way for the rational design and fabrication of multifunctional composites.

The Application Value of Serum HE4 in the Diagnosis of Lung Cancer.

Background:To investigate the clinical value of HE4 detection in the diagnosis of lung cancer and the clinical significance of combined detection with CEA, NSE and CYFRA21-1. Methods:90 cases of lung cancer, 30 cases of pulmonary tuberculosis, 30 cases of pneumonia and 30 cases of health physical examination were selected. The levels of serum HE4, CYFRA21-1, CEA and NSE were detected by electrochemiluminescence method. Statistical analysis was performed to observe the sensitivity and specificity. Results:The levels of serum HE4, CEA, NSE and CYFRA21-1 in lung cancer group were significantly higher than those in tuberculosis group and health physical examination group. There was no significant difference in the levels of HE4, CEA and NSE between the lung cancer group and the pneumonia group, the difference of CYFRA21-1 level was statistically significant (p<0.05).With health physical examination group as normal controls, the sensitivity and specificity of combined detection of HE4, CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer were 82.2% and 90.0%,and the area under the curve (AUC) was 0.907, followed by HE4 (0.867), CYFRA21-1 (0.787), CEA (0.752) and NSE (0.747). Conclusion: HE4 can be used as a serological marker for the diagnosis of lung cancer. The combined detection of HE4, CEA, NSE and CYFRA21-1 can improve the diagnosis of lung cancer. Serum HE4 levels are highly specific in distinguishing between lung cancer patients and normal population, and are equivalent to CYFRA21-1; but they are less specific than CYFRA21-1 in distinguishing lung cancer patients from pneumonia patients.

Evaluation of Red Cell Distribution Width to Lymphocyte Ratio as Potential Biomarker for Detection of Colorectal Cancer.

Background and Aim Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. Methods Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. Results RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). Conclusions RLR might serve as a potential biomarker for CRC diagnosis.

Novel cathodic photoelectrochemical immnuosensor with high sensitivity based on 3D AuNPs/ZnO/Cu2O heterojunction nanowires

A promising electrode with three-dimensional (3D) AuNPs/ZnO/Cu2O heterojunction nanowires (NWs) was developed and applied as photocathode for sensitive photoelectrochemical (PEC) immunoassay toward carcinoembryonic antigen (CEA, Ag). Firstly, Cu2O NWs were grown in situ on a Cu foil substrate to provide large specific surface area. After the modification of ZnO layer on the Cu2O NWs, the ZnO/Cu2O heterojunction structure was formed, which can increase the harvest of light energy and play a role in charge separation and transport. With further modification of gold nanoparticles (AuNPs), the good electric conductivity of the AuNPs would induce enhanced charge separation between Cu2O and ZnO. Thus, the photocurrent response of the prepared 3D AuNPs/ZnO/Cu2O NWs photocathode was significantly improved by synergistic effects of each element in the 3D structure. As a result, the fabricated cathodic PEC immunosensor exhibited high sensitivity with a low detection limit of 0.36 pg/mL (S/N = 3) for CEA detection. Furthermore, good specificity and well anti-interference capability toward real sample detection was achieved.

3D graphene/MWNTs nano-frameworks embedded Ag-Au bimetallic NPs for carcinoembryonic antigen detection

In this work, a novel electrochemical immunosensor was designed for ultrasensitive determination of carcinoembryonic antigen based on 3D-structured rGO/Ag-Au NPs. 3D-rGO-MWCNTs nanocomposites feature network structure which has a large specific surface area and excellent conductivity providing more active sites for Ag-Au bimetallic nanoparticles. At the same time, the synergistic effect of 3D-rGO-MWCNTs and Ag-Au NPs, significantly improved the electrochemical performance of the modified electrode. Due to the excellent biocompatibility of Ag-Au NPs, the antibody could be well attached to the electrode, and the immunosensor could be successfully prepared. Under the optimized conditions, the constructed immunosensor showed a wide linear range from 0.001 ng mL−1 to 80 ng mL−1 with the detection limit of 3 pg mL−1 (S/N ratio of 3). The proposed immunosensor has excellent analytical performance including good stability, reproducibility and selectivity, and was successfully applied to the detection of CEA in human serum verified its practicability.

Porous hollow carbon nanobubbles@ZnCdS multi-shelled dodecahedral cages with enhanced visible-light harvesting for ultrasensitive photoelectrochemical biosensors

Herein, novel photoactive materials, MOF-derived porous hollow carbon nanobubbles@ZnCdS multi-shelled dodecahedral cages (C@ZnCdS MSDCs)， were synthesized via continuous chemical etching, sulfurization, cation-exchange and calcination strategies. Due to the synergistic effect between the porous shells and the carbon-layer coating， C@ZnCdS MSDCs displayed superior photoelectrochemical (PEC) performance. The synthesized C@ZnCdS MSDCs were assembled onto TiO2 modified ITO electrodes to form a type-II heterostructures. Then, Au nanoparticles (NPs) were deposited on the surface of ITO/TiO2/C@ZnCdS MSDCs. Benefiting from the unique structure and performance merits of photoactive materials, a label-free PEC sensing platform based on ITO/TiO2/C@ZnCdS MSDCs/Au was successfully constructed for CEA detection. Under optimal conditions, the PEC biosensor exhibited a wide linear range (0.00005–500 ng mL−1) and low detection limit (2.28 fg mL−1). The proposed PEC biosensor also showed good stability, specificity, reproducibility and acceptability in human serum. The prepared C@ZnCdS MSDCs would be a promising photoactive material for PEC biosensors. Most importantly, this work opens up new horizons for the application of MOFs-derived hollow carbon materials in sensing.

Preoperative neutrophil-lymphocyte ratio and CEA is associated with poor prognosis in patients with synchronous colorectal cancer liver metastasis.

PurposeRecently, the neutrophil-to-lymphocyte ratio (NLR), an inflammatory response marker, has been reported to be associated with the prognosis in patients with various type of cancer. However, there have been no studies until now that have explored the prognostic role of combined detection of NLR and CEA in patients with synchronous liver-limited colorectal metastases (sCRLM).MethodsEighty-three patients who histologically diagnosed as sCRLM were selected. Their laboratory and clinical data were collected retrospectively. Using receiver operating characteristic curve analysis, the cutoff value of NLR was calculated based on which patients were assigned to a high NLR (more than 1.94) group and low NLR (less than 1.94) group. A cutoff value of 100 ng/mL for serum CEA level was used in light of the previous literature.ResultsCEA level and Poorly differentiated histology of colon cancer was significantly correlated with high NLR (P = 0.005 and P = 0.048, respectively). The multivariate analysis identified the high NLR as independent prognostic factors for OS and DFS in all patients (P = 0.010 and P = 0.006, respectively). Patients with both low levels of NLR and CEA had a significantly longer OS and DFS (P = 0.026 and P = 0.009, respectively).ConclusionIn conclusion, elevated preoperative NLR is strongly correlated with both survival and recurrence in patients who have been diagnosed with resectable sCRLM. The combination of NLR and CEA level could be a more powerful prognostic marker than NLR alone.

Glycosylation markers in cancer.

Alteration of glycosylation, a hallmark of cancer, results in the production of tumor-associated glycans or glycoproteins. These molecules are subsequently secreted or membrane-shed into the blood stream and thus serve as tumor-associated markers. Increased glycosylation in cancer is triggered by overexpression of glycoproteins that carry certain specific glycans, increase or decrease of nucleotide sugar donors and altered expression of glycosyltransferase and glycosidase enzymes. In this chapter, the biochemistry and function of glycoprotein, glycan and enzyme markers are reviewed. These glycosylation markers, applicable for detection and monitoring of cancer, include CA19-9, CA125, CEA, PSA and AFP. Because of their specific affinity to distinct sugar moieties, lectins are useful for developing assays to detect these tumor associated glycans and glycoproteins in clinical samples. As such, various enzyme-linked lectin assays (ELLA) have been developed for diagnosis, monitoring and prognosis. Because glycosylation changes occur early in cancer, the detection of tumor associated glycosylation markers using lectin based assays is an effective strategy to improve diagnosis and treatment resulting better outcomes clinically.

Simultaneous detection of carcinoembryonic antigen and neuron-specific enolase in human serum based on time-resolved chemiluminescence immunoassay.

In the clinical diagnosis of tumor, the immunological detection of single tumor markers may lead to errors and missed inspection. Therefore, it is necessary to establish an accurate and effective method for the simultaneous detection of multiple tumor markers. Thus, we developed a time-resolved chemiluminescence immunoassay (TRCLIA) to simultaneously detect carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in human serum. Horseradish peroxidase (HRP) and alkaline phosphatase (ALP) were used as the detection probes to label the monoclonal antibodies of CEA and NSE by strain-promoted azide-alkyne cycloaddition (SPAAC), respectively. Based on a sandwich immunoassay, the targets in the samples were captured by antibodies immobilized on the surface of carboxylate-modified polystyrene microspheres (CPSMS) and sandwiched by other antibodies labeled with HRP and ALP. Since HRP and ALP had different dynamic characteristics, the CEA and NSE signals were recorded at 0.5 s and 20 min, respectively, and cross-interference could be avoided effectively. The whole signal detection processes could be completed in 20 min. The linear ranges of CEA and NSE were 0.1-64 ng mL-1 and 0.05-64 ng mL-1 and the limits of detection were 0.085 ng mL-1 and 0.044 ng mL-1 (S/N = 2), respectively. Also, 45 human serum samples obtained from patients having lung disease were tested by TRCLIA and commercial chemiluminescence enzyme-linked immunoassay (CLEIA) kits with good correlation. The correlation coefficients of CEA and NSE were 0.985 and 0.970, respectively. The results demonstrated a novel, effective, reliable and convenient TRCLIA method for the clinical diagnosis of CEA and NSE. The TRCLIA method has the potential to be an effective clinical tool for the early screening of lung cancer and can be applied in clinical diagnosis.

A 3D printing-based portable photoelectrochemical sensing device using a digital multimeter.

A new enzyme-free and portable photoelectrochemical sensing method based on a homemade three-dimensional (3D) printing device was developed for accurate monitoring of a low-abundance cancer biomarker (carcinoembryonic antigen, CEA, was chosen as a model analyte in this work), coupling glucose-encapsulated liposomes with a digital multimeter readout.

Combined detection of CEA and CA125 for the diagnosis for lung cancer: A meta-analysis

This study aimed to systematically evaluate the value of combined detection of serum CEA and CA125 concentrations for the diagnosis of lung cancer. Related studies regarding the diagnosis of lung cancer were searched in PubMed, Embase, CNKI, and Wanfang using a computer. The number of patients who were true-positive, false-positive, false-negative, and true-negative were extracted from each study. Meta-analysis was performed using the Meta-Disc l.4, RevMan 5.3. Seven studies involving 2,216 cases were finally included. Regarding the diagnosis of lung cancer, the sensitivity, specificity, and diagnostic odds ratio of combined CEA and CA125 detection were higher than those of CEA detection alone. The area under the curve (AUC) of combined detection was 0.90, whereas the independently detected AUC was 0.73. Combined CEA and CA125 detection has higher diagnostic efficiency for lung cancer than CEA detection alone. The significance of combined serum CEA and CA125 detection in lung cancer is confirmed.

Detection of serum Mg7-Ag, CEA and pepsinogens combined with magnifying narrow-band imaging endoscopy for screening early gastric carcinoma in high risk patients

Detection of serum Mg7-Ag, CEA and pepsinogens combined with magnifying narrow-band imaging endoscopy for screening early gastric carcinoma in high risk patients

Cu-Au nanocrystals functionalized carbon nanotube arrays vertically grown on carbon spheres for highly sensitive detecting cancer biomarker

A three-dimensional hierarchical nanohybrid based on Cu-Au bimetallic nanocrystals integrated carbon nanotube arrays vertically grown on carbon spheres was successfully developed as an active platform for sensing application. Such nanohybrid can provide abundant active sites and act as an exceptional platform for immobilizing highly dense and well-dispersed carcinoembryonic antibody (anti-CEA) to sensitively detect CEA, an emerging biomarker of various cancer diseases. Due to the unique nanoarchitecture with altered electronic structure of Cu-Au bimetallic catalyst and enhanced interactions between components, such nanohybrid based biosensor demonstrated excellent electrochemical performance towards CEA detection with great sensitivity, wide linear detection range (0.025–25 ng/mL), very low limit of detection (0.5 pg/mL), and good selectivity. The results imply that this sensor has great potential to offer essential information for cancer diagnosis and management with great clinical importance.

Evaluation of platelet indices as diagnostic biomarkers for colorectal cancer

Altered platelet indices, including platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), have been found in various cancer types. This study aimed to evaluate the role of platelet indices as potential biomarkers for the diagnosis of colorectal cancer (CRC), and to assess the association between platelet indices and CRC clinicopathological characteristics. The study included 783 subjects with CRC, 463 subjects with colorectal adenomas (CA), and 689 control subjects from June 2015 to October 2017. All participants’ clinicopathological characteristics were collected and analyzed. Here, we found that PC, MPV and PCT levels in CRC patients were significantly higher than those in CA patients and healthy participants (p < 0.001); however, PDW level in CRC patients was significantly higher than that in healthy participants while lower than that in CA patients. Receiver-operating characteristic (ROC) analysis indicated that combined detection of PCT and CEA appears to be a more effective marker to distinguish CRC patients from CA patients, with 70% sensitivity and 83% specificity. Among CRC patients, PC and PCT levels were associated with TNM stages and tumor size; MPV and PCT levels were associated with vascular invasion. Our findings suggest that altered PC, MPV and PCT levels might serve as potential biomarkers for the diagnosis and prognosis of CRC.

Amplified electrochemiluminescence detection of CEA based on magnetic Fe3O4@Au nanoparticles-assembled Ru@SiO2 nanocomposites combined with multiple cycling amplification strategy

In this work, we designed a new strategy for ultrasensitive detection of CEA based on efficient electrochemiluminescence (ECL) quenching of Ru(bpy)32+-doped SiO2 nanocomposite by ferrocene using target recycling amplification technique. A large number of Ru@SiO2 ECL signal probe were firstly assembled on the novel magnetic core−shell Fe3O4@Au nanoparticles (NPs), then the ferrocene-labeled ECL quenching probe (Fc-probe) was linked to the magnetic NPs. Finally, numerous DNA1 sequences were produced by target CEA-triggered multiple recycling amplification and displaced the Fc-probe on the magnetic NPs, leading to significantly enhanced ECL signal for CEA detection. Because of the designed cascade signal amplification strategy, the newly developed method achieved a wide linear range of 10 fg/mL to 10 ng/mL with a low detection limit of  3.5 fg/mL. Furthermore, taking advantages of the magnetic Fe3O4@Au NPs for carring abundant signal probes, sensing target and ECL detection, the developed ECL strategy is convenient, rapid and displayed high sensitivity for CEA detection, which has great potential for analyzing the clinical samples in practical disease diagnosis applications.

Clinical application value of combined detection of serum miR-378 and miR-21 in gastric cancer

Objective: To investigate the clinical value of combined detection of serum miR-378 and miR-21 in gastric cancer (GC). Methods: Eighty-seven patients with GC and 78 patients with colorectal cancer(CRC) from National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences were selected, 83 individuals undergoing healthy physical examination were selected as the healthy controls. The levels of serum miR-378 and miR-21 were detected by quantitative real-time PCR (RT-qPCR) (result data were transformed as log2 for analysis). Results: Relative expression levels of miR-378 in the serum were -1.24, -3.25 and -2.73 in healthy controls, GC and CRC patients, respectively. Compared with the healthy controls, the levels of serum miR-378 were significantly decreased in GC and CRC patients (both P<0.05). Relative expression levels of miR-21 in the serum were 0.11, 2.34 and 2.47 in healthy controls, GC and CRC patients, respectively. Compared with the healthy controls, the levels of serum miR-21 were significantly up-regulated in GC and CRC patients (both P<0.05). Moreover, the serum level of miR-378 in GC patients was inversely associated with tumor clinical stage (P<0.05). However, the level of miR-21 showed no significant differences among patients with different clinical and pathological characteristics (all P>0.05). The area under the receiver operating characteristic curve (AUC), sensitivity and specificity of miRNA-378 to diagnose GC was 0.770, 82.0% and 66.0%, respectively, and were 0.900, 85.0%, and 88.0% of miR-21, respectively. The AUC, sensitivity and specificity of combined detection of serum miR-378 and miR-21 to diagnose GC were 0.930, 92.0% and 87.0%, respectively, while the AUC of combined detection of serum CEA and CA-199 was 0.767, the AUC of combined all of the four factors was 0.946. Conclusion: The combined detection of serum miR-378 and miR-21 have a certain effect on diagnosis of GC.

Ultrasensitive cathode photoelectrochemical immunoassay based on TiO2 photoanode-enhanced 3D Cu2O nanowire array photocathode and signal amplification by biocatalytic precipitation

Cathode photoelectrochemical immunoassay usually shows better anti-interference capacity toward real samples than anode photoelectrochemical immunoassay. However, its poor photocurrent response has greatly restricted the detection sensitivity. Herein, a promising ultrasensitive cathode photoelectrochemical immunoassay was developed based on TiO2 photoanode-enhanced 3D Cu2O nanowire array (NWA) photocathode, and coupled with signal amplification by horseradish peroxidase (HRP)-induced biocatalytic precipitation (BCP). Carcinoembryonic antigen (CEA, Ag) was used as a detection model, TiO2 nanoparticle-modified indium tin oxide (ITO) electrode served as the photoanode, and Cu2O NWAs grown in situ on Cu mesh was both the photocathode and photoelectrochemical matrix to immobilize the capture CEA antibodies (Ab1). The signal CEA antibodies (Ab2) were labeled with HRP to form Ab2-HRP bioconjugates, and employed as signal amplifiers when the specific immunoreaction occurred. The developed photoanode-enhanced cathode photoelectrochemical immunoassay has good anti-interference capability, outstanding photocurrent response, and high sensitivity for target Ag detection, which was attributed to the synergistic effects of the 3D nanostructure of Cu2O NWA photocathode, the introduction of TiO2 photoanode as counter electrode, and the signal amplification of Ab2-HRP bioconjugate-induced BCP. The developed cathode photoelectrochemical immunoassay showed a low limit of detection (0.037 pg mL−1) with a wide linear range (from 0.1 pg mL−1 to 50 ng mL−1) for CEA detection.