Cytokeratin Fragment Antigen Research Articles

Endometriosis-Associated Infertility: The Role of Biomarkers of Apoptosis and Proliferation in Early Noninvasive Diagnosis

INTRODUCTION: Endometriosis is a common disease that affects up to 15% of women in the reproductive period and leads to infertility in 25%–50% of cases. The diagnosis of endometriosis is delayed for years due to blurred and diverse clinical presentation, therefore, search for a noninvasive biomarker of endometriosis is an important problem of modern medicine. AIM: To study the significance of changes in the profile of biomarkers: regulator of Wnt/β-catenin signaling pathway (axis inhibition protein 1; AXIN-1), soluble cytokeratin 19 fragment (cytokeratin fragment antigen 21-1; CYFRA-21-1), cancer antigen 125 (carbohydrate antigen 125; CA-125) in blood plasma of patients with endometriosis-associated infertility (before surgery and in the postoperative period). MATERIALS AND METHODS: The study included two groups of female patients. The first group consisted of 20 patients of reproductive age with cystic ovarian endometriosis and infertility. All the patients underwent surgical intervention using a laparoscope and a video system, in all the patients the diagnosis of endometriosis was confirmed histologically. Three times in specified periods (before surgery, on the 10th day of the postoperative period, at 6 months), patients with cystic ovarian endometriosis and infertility were taken biomaterial (blood) with further determination of AXIN-1, CYFRA-21-1, CA-125 in blood plasma. The second group consisted of patients of reproductive age with no gynecological pathology. In the second group, biological material (blood) was taken once with further determination of AXIN-1, CYFRA-21-1, CA-125 in blood plasma. RESULTS: Based on the analysis of the measurement data and comparison of their levels, it was found that the content of the studied AXIN-1, СA-125 biomarkers in patients with cystic ovarian endometriosis and infertility was higher than in patients without gynecological pathology (p 0.05). As for CYFRA-21-1 biomarker, initially lower values were noted compared to the control group (p 0.05), however, in the postoperative period, the content of CYFRA-21-1 increased and reached values close to those of healthy patients. CONCLUSION: Determining the levels of AXIN-1, CYFRA-21-1 apoptosis biomarkers and CA-125 proliferation biomarker in blood of patients with endometriosis-associated infertility gives an insight into the pathophysiological processes in the endometrioid ovarian cysts and may be helpful in development of new noninvasive diagnostic methods and target treatment methods.

Expression and diagnostic value of serum free light chain in lung cancer.

The expression of serum free light chain (FLC) is abnormal in various diseases, but its role in lung cancer remains unclear. This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. A total of 80 lung cancer patients treated at Xiangdong Hospital, Hunan Normal University from January to December 2021 were selected as the lung cancer group. Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group. General information and serum κFLC and λFLC levels were collected for all subjects. Clinical indicators such as serum carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1) levels, tumor diameter, histological type, TNM stage, and lymph node metastasis status were recorded for lung cancer patients. The expression levels of serum FLC [κFLC, λFLC, and FLC (κ+λ)] were compared between the lung cancer group and the control group. Lung cancer patients were grouped based on gender, age, smoking history, tumor diameter, TNM stage, histological type, and lymph node metastasis to compare differences in serum κFLC and λFLC levels. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. The expression levels of serum FLC (κ+λ) and κFLC were significantly higher in the lung cancer group than those in the control group (both P<0.001), while there was no significant difference in serum λFLC levels between the 2 groups (P>0.05). There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters, histological types, or TNM stages (all P>0.05); however, serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without, with statistical significance (P=0.033). There were no significant differences in serum λFLC levels based on tumor diameter or histological type (both P>0.05), but serum λFLC levels were higher in stage III+IV and lymph node metastatic lung cancer patients compared to stage I+II and non-metastatic patients, with statistical significance (P=0.033 and P=0.019, respectively). The area under the curve (AUC) for κFLC and CEA in diagnosing lung cancer showed no significant difference (P=0.333). The combination of κFLC+CYFRA21-1 had the highest diagnostic efficacy (AUC=0.875) and sensitivity (71.3%). The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915 (95% CI 0.860 to 0.953, P<0.001). Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis. Serum FLC, particularly κFLC, has diagnostic value for lung cancer, and the combined detection of FLC, CEA, and CYFRA21-1 offers the best diagnostic efficacy.

Diagnostic value of serum squamous cell carcinoma antigen and cytokeratin fragment antigen 21-1 for sinonasal inverted papilloma: an exploratory study.

Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP. Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified. Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767. This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

A sensitive immunosensor via Pd@Au0.85Pd0.15 in situ electrocatalysis generating H2O2 for quenching electrochemiluminescence of Ir(pbi)2(acac)@Ti3C2Tx MXene-PVA

The establishment of rapid target analysis methods for cytokeratin fragment antigen 21-1 (CYFRA 21-1) is urgently needed. [Ir(pbi)2(acac)] (pbi = 2-(4-bromophenyl)-1-hydrogen -benzimidazole, acac = acetylacetonate) as traditional electrochemiluminescence (ECL) luminophores has been confined due to its non-negligible dark toxicity and poor water solubility leading to poor biocompatibility and electrical conductivity as an organic molecule. Hence, to overcome this limitation, [Ir(pbi)2(acac)] can be effectively loaded on the polyvinyl alcohol hydrogel modified Ti3C2Tx MXene surface (Ir@Ti3C2Tx-PVA) as sensing platform which can emit high ECL signals. Then, a quenching strategy was proposed to fabricate an ECL sandwich immunosensor using H2O2 as quencher molecules which can generated by Pd@Au0.85Pd0.15. Especially, the generation of O2 to H2O2 can be achieved through a two-electron (2e–) reaction pathway by Pd@Au0.85Pd0.15, to overcome the restriction that the H2O2 was virtually impossible to label or immobilize on the non-enzyme nanomaterials. The proposed ECL assay achieves a response to CYFRA 21-1 within the range of 0.1 pg/mL–100 ng/mL, with a detection limit of 8.9 fg/mL (S/N = 3). This work provided a feasible tactic to seek superior-performance ECL luminophore and quencher consequently set up a novel means to makeup ultrasensitive ECL biosensor, which extended the utilization potential of Ir(pbi)2(acac) in ECL assays.

Establishment and validation of a nomogram containing cytokeratin fragment antigen 21-1 for the differential diagnosis of intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Our study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21-1 (CYFRA21-1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). A total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram's net benefits at various threshold probabilities. Six variables, including CYFRA21-1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer-Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21-1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19-9 (Log CA19-9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21-1 was greater than that of the other variables used as diagnostic biomarkers. This study developed and validated a nomogram including CYFRA21-1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.

Effect of Anatomical Pulmonary Segmentectomy and Lobectomy under Uniportal Video-Assisted Thoracoscopic Surgery on Cardiopulmonary Function and Serum Tumor Markers in Patients with Early-Stage Non-Small Cell Lung Cancer.

In patients with early non-small cell lung cancer (NSCLC), single-port thoracoscopic anatomical segmentectomy is the primary therapeutic approach. However, the recovery of lung function is slow after operation. Conversely, anatomical segmental pneumonectomy, which excises a smaller volume of lung tissue, may facilitate more rapid functional recovery. This study aims to elucidate the comparative efficacy of these two surgical interventions by analyzing postoperative changes in cardiopulmonary function parameters and serum tumor markers. A retrospective analysis was conducted on 120 patients with NSCLC between October 2020 and October 2023. The cohort was classified into two groups based on the surgical intervention: the pulmonary segmentectomy group (n = 57), which underwent uniportal video-assisted thoracoscopic anatomical pulmonary segmentectomy, and the lobectomy group (n = 63), which received uniportal video-assisted thoracoscopic anatomical lobectomy. Surgical parameters and perioperative stress indicators were recorded for both groups of patients. Additionally, cardiopulmonary function indicators and serum biomarker levels of the patients before and 3 months after operation were compared. The operation time of the segmentectomy group was longer than that of the lobectomy group, the intraoperative blood loss was higher, and the postoperative hospital stay, chest drainage volume and drainage tube indwelling time were shorter (p < 0.001). After treatment, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and maximal voluntary ventilation (MVV) in the segmentectomy group were higher than those in the lobectomy group (p < 0.001). After treatment, stroke volume (SV) and left ventricular ejection fraction (LVEF) in the segmentectomy group were higher than those in the lobectomy group (p < 0.001). There were no significant differences in carbohydrate antigen 50 (CA50), carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) levels between the two groups after treatment (p > 0.05). The levels of Epinephrine (E), Noradrenaline (NE) and Cortisol (Cor) in the segmentectomy group were lower than those in the lobectomy group at one day after operation (p < 0.001). Compared to uniportal video-assisted thoracoscopic anatomical lobectomy, anatomical pulmonary segmentectomy for the treatment of NSCLC is more effective in reducing surgical-induced damage to cardiopulmonary function and can lower perioperative oxidative stress response. However, both surgical approaches exhibit minimal impact on serum tumor marker levels.

Diagnostic value of serum squamous cell carcinoma antigen and cytokeratin fragment antigen 21-1 for sinonasal inverted papilloma: an exploratory study

BACKGROUND: Serum tumor markers have not yet been developed for the clinical diagnosis and treatment of sinonasal inverted papilloma (SNIP), one of the most significant sinonasal tumors. Therefore, this study aimed to determine the diagnostic value of serum squamous cell carcinoma antigen (SCCA) and cytokeratin fragment antigen 21-1 (CYFRA 21-1) for SNIP. METHODS: Clinical data were obtained from 101, 56, and 116 patients with SNIP, sinonasal squamous cell carcinoma (SNSCC), and unilateral chronic rhinosinusitis (CRS), respectively. Preoperative serum SCCA and CYFRA 21-1 levels were compared, and logistic regression analyses were performed to screen serum tumor markers, which may be used to diagnose SNIP. Diagnostic cut-off values were determined using receiver operating characteristic (ROC) curves, and their diagnostic power was verified. RESULTS: Serum SCCA and CYFRA 21-1 differentiated SNIP from CRS with the cut-off values of 1.97 ng/mL and 2.64 ng/mL and the areas under the ROC curves (AUC) of 0.895 and 0.766, respectively, and the AUC of the combination of the two markers was 0.909. CYFRA 21-1 differentiated SNIP with malignant transformation from that without malignant transformation with a cut-off value of 3.51 ng/mL and an AUC of 0.938. CYFRA 21-1 distinguished SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/mL and an AUC of 0.767. CONCLUSIONS: This study provides novel potential diagnostic tools for SNIP by demonstrating the use of serum SCCA and CYFRA 21-1 in the diagnosis of SNIP.

Effect of neoadjuvant therapy on serum transforming growth factor-β, squamous cell carcinoma associated antigen, and prognosis in patients with locally advanced esophageal cancer.

It was to explore the effect of neoadjuvant therapy (NAT) on serum-related indicators and prognosis of patients with locally advanced esophageal cancer (EC). 400 EC patients were grouped as controls (295 cases, radical EC resection alone) and research group (105 cases, NAT plus radical EC resection). The levels of serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), programmed death-1 (PD-1), PD-2, transforming growth factor-β1 (TGF-β1), and squamous cell carcinoma (SCC) antigen were detected before and after treatment. The follow-up lasted for 3 years. The quality of life (QoL) was evaluated by QLQ-OES24. The recurrence rate, recurrence time, overall survival rate (SR), disease-free SR, and complication rate were compared. Compared with controls, the levels of serum CA19-9, CEA, CYFRA21-1, PD-1, PD-2, TGF-β1, and SCC were decreased, the QoL score was increased 3 years post-treatment, and the recurrence time was prolonged in the research group (P<0.05). The R0 resection rate, recurrence rate, 3-year overall SR, and disease-free SR of the two groups were 67.12% vs 85.71%, 21.36% vs 6.67%, 56.27% vs 77.14%, 29.83% vs 45.71%, respectively (P<0.05). The complication rates of the two groups were 32.54% and 29.52%, respectively (P>0.05). NAT plus radical resection of EC can effectively reduce the level of serum oncology markers in patients with locally advanced EC, reduce the postoperative recurrence rate, improve QoL and SR, and has high safety.

Development and validation of a nomogram model for lung cancer based on radiomics artificial intelligence score and clinical blood test data.

Artificial intelligence (AI) discrimination models using single radioactive variables in recognition algorithms of lung nodules cannot predict lung cancer accurately. Hence, we developed a clinical model that combines AI with blood test variables to predict lung cancer. Between 2018 and 2021, 584 individuals (358 patients with lung cancer and 226 individuals with lung nodules other than cancer as control) were enrolled prospectively. Machine learning algorithms including lasso regression and random forest (RF) were used to select variables from blood test data, Logistic regression analysis was used to reconfirm the features to build the nomogram model. The predictive performance was assessed by performing the receiver operating characteristic (ROC) curve analysis as well as calibration, clinical decision and impact curves. A cohort of 48 patients was used to independently validate the model. The subgroup application was analyzed by pathological diagnosis. A total of 584 patients were enrolled (358 lung cancers, 61.30%,226 patients for the control group) to establish the model. The integrated model identified eight potential factors including carcinoembryonic antigen (CEA), AI score, Pro-Gastrin Releasing Peptide (ProGRP), cytokeratin 19 fragment antigen21-1(CYFRA211), squamous cell carcinoma antigen(SCC), indirect bilirubin(IBIL), activated partial thromboplastin time(APTT) and age. The area under the curve (AUC) of the nomogram was 0.907 (95% CI, 0.881-0.929). The decision and clinical impact curves showed good predictive accuracy of the model. An AUC of 0.844 (95% CI, 0.710 - 0.932) was obtained for the external validation group. The nomogram model integrating AI and clinical data can accurately predict lung cancer, especially for the squamous cell carcinoma subtype.

Additional diagnostic value of the monocyte to red blood cell count ratio and the product of lymphocyte count and albumin concentration in lung cancer management.

The present study aimed to evaluate the potential of the monocyte to red blood cell count ratio (MRR), the neutrophil to red blood cell count ratio (NRR), the lymphocyte to red blood cell count ratio (LRR) and the product of lymphocyte count and albumin concentration (LA) for the diagnosis of lung cancer. The cases of 216 patients with newly diagnosed lung cancer and 184 healthy volunteers were retrospectively analysed. The MRR and NRR were found to be higher in patients with lung cancer compared with those in healthy controls, while the LRR and LA were lower. The receiver operating characteristic curve analysis revealed that of the four markers, the MRR and LA yielded a higher area under the curve (AUC) (MRR: AUC, 0.810; 95% CI, 0.768-0.847; and LA: AUC, 0.721; 95% CI, 0.674-0.764). The combination of MRR, LA, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) achieved the highest diagnostic value when compared with other single or combined markers (AUC, 0.882; 95% CI, 0.846-0.912; sensitivity, 81.9%; specificity, 81.0%). As the disease progressed, the MRR tended to increase, while LA exhibited a decreasing trend. Binary logistic regression analysis revealed an increase in the MRR, as well as in CEA and CYFRA21-1 concentrations, and a decrease in the LA, which could all be possible risk factors for lung cancer. Differences in the MRR and LA between patients with early stage (IA-IIIA) lung cancer and healthy controls were observed. Further analysis revealed that the MRR also exhibited the potential to detect early stage (IA-IIIA) lung cancer in the model. The present findings demonstrated that the MRR and LA may be used as auxiliary biomarkers for the diagnosis of lung cancer and could partly indicate disease progression.

"Gold-plated" PCN-222(Fe) and superconductive carbon black-based sandwich-type immunosensor for detecting CYFRA21-1.

Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a protein fragment dissolved in the blood after apoptosis of lung epithelial cells, which is a predictive biomarker for the diagnosis of non-small cell lung cancer (NSCLC). Detection of serum CYFRA21-1 has a significant clinical value in diagnosis, monitoring and prognosis of NSCLC. Herein, a novel electrochemical immunosensor was constructed for the sensitive detection of CYFRA21-1. First, superconductive carbon black (KB) functionalized polyethyleneimine (PEI)-gold nanoparticles (AuNPs) were covered on the surface of methylene blue (MB) and used as substrate materials to immobilize the CYFRA21-1 antibody. Then, target CYFRA21-1 was successfully detected using an electrochemical immunosensor through specific recognition of antigen and antibody. The zirconium-based metal organic framework of PCN-222(Fe) with a large pore size and three-dimensional (3D) structure can absorb abundant AuNPs through strong electrostatic interaction, which enhances the conductive properties of PCN-222(Fe) and prevents the self-aggregation of AuNPs. However, PCN-222(Fe) with peroxidase-like activity can catalyze the generation of hydroxyl free radicals (˙OH) from H2O2, which oxidized MB, leading to a decrease in the current signal. The signal response to the degradation of MB was recorded using differential pulse voltammetry (DPV). This indirect method of immunosensor offered a new strategy to address the limitations imposed by the poor conductivity of PCN-222(Fe), further enabling the amplification of the signal through the oxidative degradation of MB. Compared with traditional electrochemical immunosensors, this method has the advantages of a stable current signal and good reproducibility, providing a promising reference for the broad application of PCN-222(Fe) in electrochemical biosensors.

Co-amplification of luminol-based electrochemiluminescence immunosensors based on multiple enzyme catalysis of bimetallic oxides CoCeOx and NiMnO3 for the detection of CYFRA21-1.

The accelerated energy supply of co-reactants is an extremely effective strategy for achieving highly sensitive electrochemiluminescence analysis, and binary metal oxides would be an excellent tool for this purpose owing to the nano-enzyme acceleration of mixed metal valence states. Herein, an electrochemiluminescent (ECL) immunosensor for monitoring the concentration of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) was developed based on a co-amplification strategy triggered by two bimetallic oxides, CoCeOx and NiMnO3, with luminol as the luminophore. CoCeOx derived from an MOF exhibits a large specific surface area and excellent loading capacity as a sensing substrate, and the peroxidase properties enable the catalysis of hydrogen peroxide to provide energy supply to the underlying radicals. The dual enzymatic properties of flower-like NiMnO3 were employed as probe carriers for luminol enrichment. The peroxidase properties built on Ni2+/Ni3+ and Mn3+/Mn4+ binary redox pairs resulted in the integration of highly oxidative hydroxyl radicals, and the oxidase properties provided additional superoxide radicals via dissolved oxygen. The practically proven multi-enzyme-catalyzed sandwich-type ECL sensor easily accomplished an accurate immunoassay of CYFRA21-1, harvesting a detection limit of 0.3 pg mL-1 in the linear range of 0.001-150 ng mL-1. In conclusion, this work explores the cyclic catalytic amplification of mixed-valence binary metal oxides with nano-enzyme activity in the field of ECL and develops an effective pathway for ECL immunoassay.

Estimation of salivary and serum CYFRA 21-1 levels in patients with oral squamous cell carcinoma.

Cytokeratins are the largest sub-group of intermediate filaments and represent the most abundant proteins in epithelial cells. CYFRA 21-1 (human cytokeratin fragment antigen 21-1) is a soluble fragment of cytokeratin 19 known to increase in various malignancies. The present study is aimed to estimate salivary and serum levels of CYFRA 21-1 in oral squamous cell carcinoma (OSCC) patients and to compare them with healthy controls. A prospective, case-control study. This study included a total of 80 subjects, comprising 40 OSCC patients and 40 healthy controls. Saliva and blood samples were collected from the study population, and serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay. The statistical tests applied were independent t-test, ANOVA test for comparison, and Post hoc test for correlation. A P value of < 0.05 was considered statistically significant. A statistically significant increase in salivary and serum CYFRA 21-1 levels was observed between OSCC and control groups and with an increase in the pathological tumour node metastasis stage and histopathological grade of OSCC. On correlating salivary and serum CYFRA 21-1 values, there were 3-fold higher salivary levels than serum. CYFRA 21-1 can be suggested as a tumour marker that can be used for the early diagnosis of the OSCC. Further prospective studies with a larger sample size and advanced techniques recommended before CYFRA 21-1 can be recommended for routine clinical use.

A Novel Signal-On Electrochemiluminescence Immunosensor for the Detection of NSCLC Antigen Biomarker Based on New Co-Reaction Accelerators.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with substantial morbidity and mortality. Herein, a new signal-on electrochemiluminescence (ECL) immunosensor based on multiple amplification strategies is constructed for ultrasensitive detection of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) biomarker related to NSCLC. Polyethyleneimine (PEI) functionalized MXene is decorated with NiMn layer double hydroxide (NiMn LDH) to form MXene-PEI-NiMn LDH composite. Specially, the La-MOF@ZIF-67 bimetallic organic framework (named as LZBM) and MXene-PEI-NiMn LDH both served as coreaction accelerators to improve the ECL emission of the luminol-H2 O2 system. To be specific, Au nanoparticles (AuNPs) coated MXene-PEI-NiMn LDH is applied to immobilize primary CYFRA21-1 antibody (Ab1 ), while AuNPs decorated LZBM was used for the loading of luminol and secondary CYFRA21-1 antibody (Ab2 ) to form tracer label. Therefore, the ECL signal of the sandwich-type immunosensor is significantly enhanced due to the high loading capability for luminol and the synergistic catalytic ability for the decomposition of H2 O2 into reactive oxygen species (ROS). Under the optimal experimental conditions, the ECL immunosensor exhibited good analytical performances for CYFRA21-1 detection with a wide linear range (100 fg mL-1 -100 ng mL-1 ) and a low limit of detection (85.20 fg mL-1 ), providing a promising method for early diagnosis of NSCLC.

Diagnostic value of combination of exfoliative cytology with CA125, CEA, NSE, CYFRA21-1 and CA15-3 for lung cancer

Abstract Background: To explore the diagnostic value of combination of exfoliative cytology with detection of tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), neuron specific enolase (NSE), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and CA15-3 for lung cancer. Methods: A total of 256 patients were enrolled, including 164 males and 92 females aged (64.51±22.68) years old. Among them, 189 patients (100 males and 89 females) were randomly selected as Tumor group, and the remaining 67 patients were used for validation. Another 514 healthy people receiving physical examination in our hospital during the same period were selected, from which 397 cases (266 males and 131 females) were randomly selected as No Tumor group, and the remaining 117 cases were used for validation. The biochemical criteria were detected in all subjects. The diagnostic value of each index for lung cancer was analyzed using receiver operating characteristic (ROC) curves. Results: The results of ROC curve analysis revealed that in Tumor group, the area under curve (AUC) of exfoliative cytology, CA125, CYFRA21-1, CA15-3, CEA and NSE was ≥0.7, while that of CA72-4, CA19-9, TSGF, AFP, CA242, SCCAg and CA50 was &lt;0.7. The indices in each factor were comprehensively assessed, and then exfoliative cytology, CA125, CA15-3, CYFRA21-1, CEA and NSE were screened to establish the lung cancer prediction model. The diagnostic value was comparable between the prediction model and the combined detection of 9 indices (Z=1.682, P=0.079). Conclusions: The lung cancer prediction model balances sensitivity and specificity without reducing the diagnostic efficiency.

Electrochemical immunosensor for individual and simultaneous determination of Cytokeratin fragment antigen 21-1 and Neuron-specific enolase using carbon dots-decorated multiwalled carbon nanotube electrode

In this approach, we fabricated a sandwich-type electrochemical immunosensor for individual and simultaneous sensing of cytokeratin fragment antigen 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) using the multiple-label concept. In this report, carbon dots (CDs) were prepared from citric acid and ethylenediamine (EDA). A hybrid EDA-CDs-MWCNTs composites were prepared and then decorated with gold nanoparticles (AuNPs). The obtained hybrid composites were used as an immunosensing platform. Furthermore, AuNPs decorated EDA-CDs-MWCNTs was carefully loaded with reactive dye (orange G and carminic acid) and utilized as signal labels. The surface morphology and the electrochemical properties of the modified SPCE were studied carefully. The linear range for the individual and simultaneous detection was 0.002–10 ng mL−1 for the CYFRA 21-1 and NSE and the detection limits (LODs) were 0.22 pg mL−1 and 0.15 pg mL−1 for the individual detection while 0.25 pg mL−1 and 0.20 pg mL−1 for simultaneous detection, respectively. This developed immunoassay was utilized for the assessment of two markers in the serum sample with reasonable consequences.

Clinical Value of Pleural Effusion and Serum MMP-3 and CYFRA21-1 Combined with ADA in Differential Diagnosis of Pleural Exudative Effusion.

Objective The aim of the study is to investigate the clinical value of matrix metalloproteinases-3 (MMP-3) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) combined with adenosine deaminase (ADA) in pleural effusion and serum in benign and malignant pleural exudative effusion (PEE). Methods A total of 119 adult patients with PEE admitted in our hospital from May 2018 to October 2021 were selected. According to the patient's condition, the patients were divided into the benign group (n = 75) and the malignant group (n = 44). The levels of MMP-3, CYFRA21-1, and ADA in pleural effusion and serum were detected. The receiver operating characteristic (ROC) curve was used to analyze the individual and combined predictive value of MMP-3, CYFRA21-1, and ADA levels. Results In the malignant group, the pleural effusion and serum MMP-3 and CYFRA21-1 levels were higher than those in the benign group and the ADA levels were lower than those in the benign group (P < 0.05). In the malignant group, the positive detection rate of pleural effusion and serum MMP-3 and CYFRA21-1 was higher than that in the benign group and the positive detection rate of pleural effusion and serum ADA were lower than that in the benign group (P < 0.05). The AUC of pleural effusion MMP-3, serum MMP-3 and the combination of them in the diagnosis of PEE were 0.764, 0.722 and 0.810, respectively. The AUC of pleural effusion CYFRA21-1 and serum CYFRA21-1 and combination of them in the diagnosis of PEE were 0.776, 0.748 and 0.822, respectively. The AUC of pleural effusion ADA, serum ADA and their combination in differential diagnosis of PEE were 0.762, 0.737 and 0.836, respectively. The AUC of pleural effusion and serum of MMP-3 and CYFRA21-1 combined with ADA for differential diagnosis of PEE was 0.923. Conclusions The diagnostic efficacy of MMP-3 combined with CYFRA21-1 and ADA in pleural effusion and serum for benign and malignant PEE are better than single index, which has certain clinical values for the selection of early intervention scheme for PEE patients.

Detection of CYFRA21-1 in serum by electrochemical immunosensor based on nanocomposite consisting of AuNPs@CMK-3@CMWCNTs

An electrochemical immunosensor based on the modification of nanocomposite was constructed to detect the lung cancer marker Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1). Ordered mesoporous carbon CMK-3 was selected to mix with carboxylated multi-walled carbon nanotubes (CMWCNTs), and their combination could enhance electron transfer efficiency and amplify the electrochemical signal. Furthermore, aurum nanoparticles (AuNPs) were further mixed with the hybrid carbon nanomaterials, which bind antibodies via Au-S bonds and provide numerous of binding sites for antibodies. Finally, CYFRA21-1 could be detected by specific immune response between antigen and antibody by improving the immunosensor sensitivity. The characterization of scanning electron microscopy (SEM) showed that AuNPs were embedded on the surface and interstices of CMK-3@CMWCNTs. The curves of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed that the immunsensor was successfully constructed. The constructed immunosensor had a linear range of 0.5 pg/mL to 105 pg/mL for the detection of CYFRA21-1 in serum, and the correlation coefficient (r) was 0.998, with a detection limit of 0.2 pg/mL. Thus, this method is selective and sensitive for getting the accurate and reliable detection results and provides a new method for the CYFRA21-1 ultrasensitive detection in serum.

Effects of Bevacizumab Combined with Chemotherapy on CT, CyFRA21-1, and ProGRP and Prognosis of Lung Cancer Patients under Nursing Intervention.

Objective Molecular targeted drug therapy and chemotherapy are the main treatments for advanced non-small-cell lung cancer, and the combination of both has advantages in prolonging patients' progression-free survival and overall survival. This study investigated the effects of bevacizumab combined with chemotherapy under nursing intervention on CT, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), and gastrin-releasing peptide precursor (ProGRP) and prognosis of lung cancer patients. Methods 102 patients with non-small-cell lung cancer admitted to our hospital from January 2018 to May 2019 were divided into observation group and control group, with 51 cases each. The control group was treated with basic chemotherapy, and the observation group was treated with bevacizumab in combination with the control group, and both groups used nursing interventions. The clinical effects, CYFRA21-1 and ProGRP levels, baseline data, CT parameters, 24-month cumulative survival, and the effects of CYFRA21-1 and ProGRP on long-term survival and lung function were compared. Results The disease control rate of the observation group was 94.12%, which was significantly higher than that of the control group (76.47%); after 7 d, 30 d, 60 d, and 90 d of treatment, the levels of CYFRA21-1 and ProGRP were statistically downregulated. The difference in lymph node metastasis, lesion diameter, plain Eff-Z, venous stage, and arterial stage normalized iodine concentrations (NIC) was statistically significant; the survival rate at 24 months in the observation group was 74.51% (38/51); the cumulative survival rate at 24 months in the control group was 52.94% (27/51), and the difference was statistically significant (X2 = 4.980, P = 0.026). The cumulative survival rate at 24 months was significantly lower in patients with high expression of CYFRA21-1 and ProGRP compared with those with low expression of CYFRA21-1 and ProGRP. After treatment, in the observation group, the forceful spirometry (FVC), forceful expiratory volume in one second (FEV1), and FEV1/FVC levels were significantly different from those before treatment and were significantly different from those in the control group. Conclusion Bevacizumab in combination with standard chemotherapy regimens with nursing interventions could benefit patients with advanced non-small-cell lung cancer and had a good prospect of application.

Prognostic Evaluation of CT Imaging Big Data-Assisted Arterial Chemoembolization Combined with 125I Seed Implantation for Non-Small-Cell Lung Cancer.

Objective To investigate the prognostic impact of computed tomography (CT) imaging big data-assisted arterial chemoembolization combined with iodine 125 (125I) seed implantation on patients with non-small-cell lung cancer (NSCLC). Methods A total of 116 patients with intermediate and advanced NSCLC hospitalized in our hospital from August 2019 to August 2020 were selected and divided into a control group and an experiment group (58 cases in each group) by random number table method for the study. The patients in the experiment group were treated with CT imaging big data-assisted arterial chemoembolization combined with 125I seed implantation, while the patients in the control group were treated with arterial chemoembolization alone, with the use of gemcitabine combined with cisplatin (GP) in chemotherapy. The prognostic impact was determined by analyzing recent efficacy; the incidence of adverse effects; tumor size and CT perfusion parameters including blood volume (BV), blood flow (BF), and permeability surface (PS); frailty state and quality of life; and the levels of serum tumor markers including carcinoembryonic antigen (CEA), glycoconjugate antigen 125 (CA125), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), microRNA- (miRNA-) 137, and miR-379-5p. In addition, frailty status was evaluated using the Fried frailty phenotype (FP) scale, and quality of life was determined according to Karnofsky Performance Status (KPS) score. Kaplan-Meyer (KM) method was used to analyze the survival rate of NSCLC patients after a 12-month follow-up. Results The remission rate in the experiment group (77.59%) was higher than that in the control group (56.90%) (P < 0.05). Tumor size, BV, BF, PS, serum CEA and CA125 levels, and FP value in both groups were dramatically reduced after treatment compared with before treatment, especially in the experiment group after 1 and 3 months of treatment (P < 0.05). Meanwhile, the serum miR-137 and miR-379-5p levels and KPS scores in both groups were higher after treatment than before treatment, especially in the experiment group after 1 and 3 months of treatment (P < 0.05). However, there was no significant difference in the incidence of nausea and vomiting, alopecia, diarrhea, myelosuppression, and hemoptysis of NSCLC patients in both groups after treatment (P > 0.05). Further, the 12-month survival rate of NSCLC patients was higher in the experiment group (84.21%) than in the control group (64.29%) (P < 0.05). Conclusion CT imaging big data-assisted arterial chemoembolization combined with 125I seed implantation for NSCLC can improve recent efficacy and the prognosis of NSCLC patients by inhibiting tumor progression with a certain degree of safety.