A combination of radiomic features, clinic characteristics, and serum tumor biomarkers to predict the possibility of the micropapillary/solid component of lung adenocarcinoma.

BACKGROUND: Invasive lung adenocarcinoma with MPP/SOL components has a poor prognosis and often shows a tendency to recurrence and metastasis. This poor prognosis may require adjustment of treatment strategies. Preoperative identification is essential for decision-making for subsequent treatment. OBJECTIVE: This study aimed to preoperatively predict the probability of MPP/SOL components in lung adenocarcinomas by a comprehensive model that includes radiomics features, clinical characteristics, and serum tumor biomarkers. DESIGN: A retrospective case control, diagnostic accuracy study. METHODS: This study retrospectively recruited 273 patients (males: females, 130: 143; mean age ± standard deviation, 63.29 ± 10.03 years; range 21-83 years) who underwent resection of invasive lung adenocarcinoma. Sixty-one patients (22.3%) were diagnosed with lung adenocarcinoma with MPP/SOL components. Radiomic features were extracted from CT before surgery. Clinical, radiomic, and combined models were developed using the logistic regression algorithm. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC). Studies were scored according to the Radiomics Quality Score and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines. RESULTS: The radiomics model achieved the best AUC values of 0.858 and 0.822 in the training and test cohort, respectively. Tumor size (T_size), solid tumor size (ST_size), consolidation-to-tumor ratio (CTR), years of smoking, CYFRA 21-1, and squamous cell carcinoma antigen were used to construct the clinical model. The clinical model achieved AUC values of 0.741 and 0.705 in the training and test cohort, respectively. The nomogram showed higher AUCs of 0.894 and 0.843 in the training and test cohort, respectively. CONCLUSION: This study has developed and validated a combined nomogram, a visual tool that integrates CT radiomics features with clinical indicators and serum tumor biomarkers. This innovative model facilitates the differentiation of micropapillary or solid components within lung adenocarcinoma and achieves a higher AUC, indicating superior predictive accuracy.

A new tool to predict aggressive lung cancer types before surgeryWe developed a tool to help doctors determine whether lung cancer is one of the more dangerous types, called micropapillary (MPP) or solid (SOL) patterns, before surgery. These patterns can be more harmful and spread quickly, so knowing they are there can help doctors plan the best treatment. We looked at the cases of 273 lung cancer patients who had surgery and found that 61 of them had these aggressive cancer types. To predict these patterns, we used a computer process known as logistic regression, analyzing CT scan details, health information, and blood tests for cancer markers. Based on CT scans, our tool was very good at predicting whether these patterns were present in two patient groups. However, predictions using only basic health information like the size of the tumor and whether the patient smoked needed to be more accurate. We found a way to make our predictions even better. Combining all information into one chart, known as a nomogram, significantly improved our ability to predict these dangerous cancer patterns. This combined chart could be a big help for doctors. It gives them a clearer picture of the cancer's aggressiveness before surgery, which can guide them to choose the best treatment options. This approach aims to offer a better understanding of the tumor, leading to more tailored and effective treatments for patients facing lung cancer.

Prognostic value of serum oncomarkers for patients hospitalized with acute exacerbation of interstitial lung disease.

BACKGROUND: Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear. OBJECTIVE: To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes. DESIGN: Retrospective study. METHODS: The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis. RESULT: Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP. CONCLUSION: CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD.

A preliminary study on the reference intervals of serum tumor marker in apparently healthy elderly population in southwestern China using real-world data.

BACKGROUND: The aim is to establish and verify reference intervals (RIs) for serum tumor markers for an apparently healthy elderly population in Southwestern China using an indirect method. METHODS: Data from 35,635 apparently healthy elderly individuals aged 60 years and above were obtained in West China Hospital from April 2020 to December 2021. We utilized the Box-Cox conversion combined with the Tukey method to normalize the data and eliminate outliers. Subgroups are divided according to gender and age to examine the division of RIs. The Z-test was used to compare differences between groups, and 95% distribution RIs were calculated using a nonparametric method. RESULTS: In the study, we observed that the RIs for serum ferritin and Des-γ-carboxy prothrombin (DCP) were wider for men, ranging from 64.18 to 865.80 ng/ml and 14.00 to 33.00 mAU/ml, respectively, compared to women, whose ranges were 52.58 to 585.88 ng/ml and 13.00 to 29.00 mAU/ml. For other biomarkers, the overall RIs were established as follows: alpha-fetoprotein (AFP) 0-6.75 ng/ml, carcinoembryonic antigen (CEA) 0-4.85 ng/ml, carbohydrate antigen15-3 (CA15-3) for females 0-22.00 U/ml, carbohydrate antigen19-9 (CA19-9) 0-28.10 U/ml, carbohydrate antigen125 (CA125) 0-20.96 U/ml, cytokeratin 19 fragment (CYFRA21-1) 0-4.66 U/ml, neuron-specific enolase (NSE) 0-19.41 ng/ml, total and free prostate-specific antigens (tPSA and fPSA) for males 0-5.26 ng/ml and 0-1.09 ng/ml. The RIs for all these biomarkers have been validated through our rigorous processes. CONCLUSION: This study preliminarily established 95% RIs for an apparently healthy elderly population in Southwestern China. Using real-world data and an indirect method, simple and reliable RIs for an elderly population can be both established and verified, which are suitable for application in various clinical laboratories.

Multidimensional biomarker approach integrating tumor markers, inflammatory indicators, and disease activity indicators may improve prediction of rheumatoid arthritis-associated interstitial lung disease.

INTRODUCTION: Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). METHODS: Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. RESULTS: The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. CONCLUSION: The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes.

Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CONCLUSION: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

A Co-Reactive Immunosensor Based on Ti3C2Tx MXene@TiO2-MoS2 Hybrids Promoting luminol@Au@Ni-Co NCs Electrochemiluminescence for CYFRA 21-1 Detection.

The construction of assays is capable of accurately detecting cytokeratin-19 (CYFRA 21-1), which is critical for the rapid diagnosis of nonsmall cell lung cancer. In this work, a novel electrochemiluminescence (ECL) immunosensor based on the co-reaction promotion of luminol@Au@Ni-Co nanocages (NCs) as ECL probe by Ti3C2Tx MXene@TiO2-MoS2 hybrids as co-reaction accelerator was proposed to detect CYFRA 21-1. Ni-Co NCs, as a derivative of Prussian blue analogs, can be loaded with large quantities of Au NPs, luminol, and CYFRA 21-1 secondary antibodies due to their high specific surface area. To further improve the sensitivity of the developed ECL immunosensor, Ti3C2Tx MXene@TiO2-MoS2 hybrids were prepared by in situ growth of TiO2 nanosheets on highly conductive Ti3C2Tx MXene, and MoS2 was homogeneously grown on Ti3C2Tx MXene@TiO2 surfaces by the hydrothermal method. Ti3C2Tx MXene@TiO2-MoS2 hybrids possess excellent catalytic performance on the electro-redox of H2O2 generating more O2·- and obtaining optimal ECL intensity of the luminol/H2O2 system. Under the appropriate experimental conditions, the quantitative detection range of CYFRA 21-1 was from 0.1 pg mL-1 to 100 ng mL-1, and the limit of detection (LOD) was 0.046 pg mL-1. The present sensor has a lower LOD with a wider linear range, which provides a new analytical assay for the early diagnosis of small-cell-type lung cancer labels.

Clinical value of serum DJ-1 in lung adenocarcinoma.

Objective: DJ-1 is an oncoprotein secreted by cancer cells. However, the physiological and pathological significance of DJ-1 secretion is not clearly understood. This study investigated the clinical value of serum DJ-1 in lung adenocarcinoma (LUAD). Methods: The study involved 224 LUAD patients, 110 patients with benign pulmonary disease and 100 healthy controls from the First Affiliated Hospital of Nanjing Medical University. We detected the expression of DJ-1 in lung cell lines in vitro. Meanwhile, serum concentrations of DJ-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA21-1) were measured. The diagnostic performance of LUAD was obtained using receiver operating characteristic (ROC) curves. Kaplan-Meier, univariate and multivariate Cox regression analyses were performed for progression-free survival (PFS). Results: DJ-1 was highly expressed in LUAD cell lines. Serum DJ-1 levels were significantly higher in the LUAD group compared to the benign pulmonary disease group (5.04 vs. 3.66 ng/mL, P < 0.001) and healthy controls (5.04 vs. 3.51 ng/mL, P < 0.001). DJ-1 levels were associated with gender (P = 0.002), smoking history (P = 0.042) and lymph node metastasis (P = 0.040). ROC curve analysis of DJ-1 revealed an area under the curve (AUC) of 0.758 (95% CI [0.714-0.803], P < 0.001) with a sensitivity of 63.8% and specificity of 78.6% at a cutoff value of 4.62 ng/mL for the detection of LUAD. Univariate and multivariate analyses confirmed that the preoperative serum DJ-1 level, tumor stage and smoking history were independent prognostic factors of PFS. Conclusion: Our study is the first to explore the clinical value of serum DJ-1 in LUAD comprehensively. Serum DJ-1 could be a potential diagnostic and prognostic biomarker for LUAD.

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.

New insights into the diagnostic characteristics and clinical application of serum biomarkers for lung cancer, and human epididymis protein 4 as a new biomarker?

The value of serum tumor biomarkers used for lung cancer diagnosis is still controversial in clinical practice. This study aimed to further dissect and evaluate the clinical value of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1) together with a potential new biomarker, the human epididymis protein 4 (HE4) for lung cancer diagnosis, in a large cohort of a Chinese population. Ostensibly healthy individuals, as well as those with benign non-cancerous diseases, benign tumors, lung cancers, and other types of malignancies, were enrolled in the study. Serum ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were analyzed using the chemiluminescence immunoassay. Data were analyzed utilizing the SPSS and GraphPad Prism software. Detailed dissection of the diagnostic characteristics of serum 6 biomarkers on lung cancer was performed. All 6 biomarkers showed capabilities in characterizing lung cancer from other diseases. ProGRP and NSE were highly specific to small cell lung cancer (SCLC); SCC-Ag was a fair biomarker for NSCLC, specifically SCC histotype; CEA showed specificity to SCLC, followed by NSCLC; CYFRA21-1 was a good biomarker for both SCLC and NSCLC; HE4 showed high specificity to SCLC. For NSCLC characterization, CYFRA21-1+HE4+CEA was the best combinatory pattern in the terms of diagnostic performance (AUC=0.8110). The best combinatory analysis for SCLC was ProGRP+NSE+HE4 (AUC=0.9282). Patients with advanced stage, larger tumor, males, and age 50 or older had higher serum biomarkers levels than those with early stage, smaller tumor, females, and age under 50. Six biomarkers had capabilities in characterizing lung cancer with high or fair diagnostic performance. HE4 is a potential biomarker for both SCLC and NSCLC diagnosis, which merits further investigation.

CYFRA21-1 is a more sensitive biomarker to assess the severity of pulmonary alveolar proteinosis.

BACKGROUND: Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient's condition. METHODS: APAP patients numbering 151 were enrolled in this study. All patients' severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1-2 and 3-5 through receiving operating characteristics (ROC) curve. RESULTS: Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1-2 and 3-5) showed an optimal cutoff of LDH of over 203 U/L (< 246 U/L), CEA of over 2.56 ug/L (< 10 ug/L), and CYFRA21-1 of over 5.57 ng/ml (> 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748-0.882], sensitivity: 0.606, specificity: 0.877). CONCLUSION: Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Prognostic Impact of Pretreatment Serum CYFRA Status in 1047 Patients with Esophageal Squamous Cell Carcinoma Who Underwent Radical Resection: A Japan Esophageal Society Promotion Research.

PURPOSE: The prognostic significance of pretreatment serum C-terminus of cytokeratin 19 (CYFRA21-1, CYFRA) status was evaluated in the patients with surgically treated esophageal squamous cell carcinoma. METHODS: A total of 1047 patients with surgically treated esophageal cancer were enrolled in a multi-institutional study promoted by the Japanese Esophageal Society. This study included an up-front surgery group (n = 412), a neoadjuvant chemotherapy (NAC) group (n = 486), and a neoadjuvant chemoradiation/radiation therapy (NACRT/RT) group (n = 149). The pretreatment CYFRA status was analyzed to assess prognostic significance using multivariate analysis according to treatment modalities. RESULTS: The CYFRA-positive group was significantly associated with deep tumor. Univariate analysis showed that the overall survival of the CYFRA-positive group was significantly worse than that of the CYFRA-negative group, but the difference was not significant in the multivariate analysis. CYFRA was an independent risk factor for poor prognosis just in the NACRT/RT group. CONCLUSIONS: The CYFRA-positive group was associated with deep tumor and poor survival. Pretreatment CYFRA was not an independent risk factor for poor prognosis in the up-front surgery group or NAC group. It was an independent risk factor for poor prognosis just in the NACRT/RT group.

A sandwiched photoelectrochemical biosensing platform for detecting Cytokeratin-19 fragments based on Ag2S-sensitized BiOI/Bi2S3 heterostructure amplified by sulfur and nitrogen co-doped carbon quantum dots.

A sandwiched photoelectrochemical (PEC) immunosensor based on BiOI/Bi2S3/Ag2S was designed for the quantitative detection of cytokeratin-19 fragments (CYFRA21-1) in serum. In this work, due to the intervention of the narrow band gap Bi2S3, the absorption of the light source by the BiOI/Bi2S3 heterostructure has been significantly enhanced. Meanwhile, the matched band structure of BiOI, Bi2S3 and Ag2S promoted the rapid transfer of electrons between the conduction bands and effectively inhibited the recombination of electron-hole pairs, thus enhanced the photoelectric signals. Sulfur and nitrogen co-doped carbon quantum dots (S,N-CQDs) with up-conversion luminescence properties provided more light energy for the base materials. On the other hand, S,N-CQDs were combined with Ab2 through polydopamine (PDA), as secondary antibody labels, further enhanced the sensitivity of the sensor. Herein, the linear range of the sensor was from 0.001 to 100 ng mL-1 and the detection limit was 1.72 pg mL-1. In addition, the sensor provides a feasible way for the detection of tumor markers due to its excellent selectivity, repeatability and good stability.

An ultrasensitive ratiometric immunosensor based on the ratios of conjugated distyrylbenzene derivative nanosheets with AIECL properties and electrochemical signal for CYFRA21-1 detection.

Aggregation-induced electrochemiluminescence reagent, a distyrylbenzene derivative with donor-acceptor conjugated nanosheet structure, namely TPAPCN, was used as a trace label and modified on the electrode through the formation of classical sandwich complex of antibody-antigen-antibody in this work. In aggregate state, TPAPCN with twisted structure was limited in nanometer space through intermolecular π - π stacking interactions, which not only restricts the intramolecular motions but also combines a large number of singlet excitons to greatly trigger electrochemiluminescence (ECL). The ECL signal of this system enhanced with more captured cytokeratin 19 fragment 21-1 (CYFRA21-1) on the modified electrode. Three-dimensional graphene/platinum nanoparticles with large specific surface, and excellent electroconductivity and biocompatibility were prepared and acted as excellent carriers for thionine handling (3D-GN/PtNPs/Th), which was employed for improving the loading of antibodies and generating internal electrochemical signal. Consequently, a novel ratiometric sandwich immunosensor for CYFRA21-1 detection was fabricated based on TPAPCN and 3D-GN/PtNPs/Th, that is, a rapid and reliable detection was achieved through the ratio between ECL and electrochemical signals. The prepared sensor performed good linearity in the range of 50 fg/mL to 1 ng/mL with a detection limit as low as 16 fg/mL. Moreover, the detection results revealed well in the analysis of human serum samples, demonstrating a significant application for clinical monitoring and biomolecules detection.

The Role of Change Rates of CYFRA21-1 and CEA in Predicting Chemotherapy Efficacy for Non-Small-Cell Lung Cancer.

BACKGROUND: Cytokeratin 19 fragment 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) are effective prognostic biomarkers for lung cancer. This study investigated the predictive effects of change rates of CYFRA21-1 and CEA before and after the first cycles of chemotherapy on advanced IIIb/IIIc or IV stage non-small-cell lung cancer (NSCLC) patients. METHODS: Data of 103 NSCLC patients who received chemotherapy in Zhejiang Provincial People's Hospital from February 2018 to November 2020 were retrospectively analyzed. All patients received platinum doublet chemotherapy for at least 2 cycles. CYFRA21-1 and CEA levels of patients were detected before and after the first chemotherapy cycle, respectively. After the second cycle, the efficacy was evaluated, and patients were divided into the disease control (DC) and progressive disease (PD) groups. The generalized linear model (GLM) and linear trend test assessed the relationship between change rates of CYFRA21-1 and CEA levels and chemotherapeutic efficacy before and after chemotherapy. Moreover, the receiver operating characteristic (ROC) curve determined the predictive value of change rates of CYFRA21-1 and CEA on chemotherapeutic efficacy. RESULTS: After the second chemotherapeutic cycle, there were 92 patients in the DC group and 11 in the PD group. GLM and linear trend test both indicated that change rates of CYFRA21-1 and CEA were inversely correlated with chemotherapeutic efficacy for NSCLC. Change rates of CYFRA21-1 and CEA were used to predict area under the ROC curve of chemotherapeutic efficacy (0.87, 0.71-1.00), which is better than single index prediction of CYFRA21-1 (0.71, 0.49-0.94) or CEA change rate (0.85, 0.69-1.00) (p < 0.001). CONCLUSION: Before and after chemotherapy of the first cycle for advanced NSCLC patients, combining serum CYFRA21-1 and CEA levels could increase sensitivity and specificity to predict the chemotherapeutic efficacy and guide the following therapy of advanced NSCLC patients.

Elevated serum CYFRA 21-1 level as a diagnostic marker for thymic carcinoma.

BACKGROUND: No useful tumor markers have been identified for the diagnosis of thymic carcinomas. Serum cytokeratin 19 fragment, measured using the CYFRA 21-1 immunoassay, is used as a tumor marker for squamous cell carcinomas in various malignant tumors. Here, we evaluated the value of CYFRA 21-1 in diagnosing thymic carcinoma. METHODS: We retrospectively reviewed 94 patients with pathological diagnoses of thymic carcinoma or thymoma (32 and 62 patients, respectively) who were referred to our departments between January 2000 and March 2019. Primary outcomes included tumor marker levels and their diagnostic accuracy. RESULTS: Patients with thymic carcinoma were significantly more likely to be male (thymic carcinoma, 68.8%; thymoma, 40.3%; p = 0.02), have an advanced TNM stage (p < 0.01), and a significantly higher CYFRA 21-1 level than those with thymoma (thymic carcinoma: median = 4.2 ng/ml; interquartile range [IQR] = 2.1-6.1 ng/ml vs. thymoma: median = 1.2 ng/ml; IQR = 0.9-1.7 ng/ml; p < 0.01). Receiver operating characteristic curves demonstrated that the area under the curve for CYFRA 21-1 to distinguish thymic carcinoma from thymoma was 0.86 (95% confidence interval [CI]: 0.74-0.93; cutoff = 2.7 ng/ml; sensitivity = 68.8%; specificity = 95.2%). Multivariable analysis demonstrated that CYFRA 21-1 (odds ratio = 25.6; 95% CI: 4.6-141.6; p < 0.01) was an independent predictor for thymic carcinoma after adjusting for TNM stage. CONCLUSIONS: Serum CYFRA 21-1 level may help in diagnosing thymic carcinoma.

Word Embedding Reveals Cyfra 21-1 as a Biomarker for Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD. Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding. METHODS: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD. RESULTS: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, P = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219, P = 0.015). CONCLUSION: Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. METHODS: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. RESULTS: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). CONCLUSIONS: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.

Diagnostic value of conventional tumor markers in young patients with pulmonary nodules.

BACKGROUND: Lung cancer is one of the most common malignancies, and there is a trend of increasing incidence in young patients. The preoperative diagnosis of pulmonary nodules is mainly based on the combination of imaging and tumor markers. There is no relevant report on the diagnostic value of tumor markers in young pulmonary nodules. Our study was designed to explore the value of five tumor markers in young patients with pulmonary nodules. METHODS: We reviewed the medical records of 390 young patients (age ≤45 years) with pulmonary nodules treated at two separate centers from January 1, 2015, to January 1, 2021. Malignant pulmonary nodules were confirmed in 318 patients, and the other 72 patients were diagnosed with benign pulmonary nodules. The gold standard for diagnosis of pulmonary nodules was surgical biopsy. The conventional serum biomarkers included cytokeratin 19 (CYFRA21-1), pro-gastrin-releasing-peptide (ProGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma-associated antigen (SCCA). The diagnostic values of five tumor markers were analyzed by receiver operating characteristic (ROC) curves. RESULTS: There were no significant differences in the expression of five tumor markers between the groups (p > 0.05). Single tumor marker (CYFRA21-1, ProGRP, CEA, NSE, and SCCA) showed a limited value in the diagnosis of malignant pulmonary nodules, with the AUC of 0.506, 0.503 0.532, 0.548, and 0.562, respectively. The AUC of the combined examination was only 0.502~0.596, which did not improve the diagnostic value. CONCLUSIONS: Five conventional tumor markers had a limited diagnostic value in young patients with pulmonary nodules.

Rationally engineered high-performance BiVO4/Ag3VO4/SnS2 photoelectrodes for ultrasensitive immunosensing of CYFRA21-1 based on HRP-tyramine-triggered insoluble precipitates.

A photoelectrochemical (PEC) biosensor capable of detecting cytokeratin 19 fragment 21-1 (CYFRA21-1) was optimized by taking advantage of the powerful conjugate repeats of horseradish peroxidase and tyramine (HRP-tyramine)-triggered enzymatic biocatalytic precipitation (BCP) on high-performance BiVO4/Ag3VO4/SnS2 photoelectrodes. Compared with the ubiquitous BCP strategy, we identified a design supporting conjugate repeats generated by HRP and tyramine-triggered immeasurable insoluble precipitates in the presence of hydrogen peroxide and 4-chloro-1-phenol (4-CN), and the steric hindrance improved sensitivity. Moreover, by virtue of BiVO4, Ag3VO4, SnS2 excellent level matching structure and chemical stability, a heterojunction (BiVO4/Ag3VO4/SnS2) with high light absorption efficiency has been successfully prepared. The novel heterostructure system of BiVO4/Ag3VO4/SnS2 with high detection current and low background signal exhibited high-performance PEC determination. Generally, the hitherto untapped biosensor resource realized the sensitive detection of CYFRA21-1 with a wide linear range from 50 fg/mL to 200 ng/mL, and a detection limit of 15 fg/mL, which illustrated the potential for biotechnological applications.

Age-stratified and gender-specific reference intervals of six tumor markers panel of lung cancer: A geographic-based multicenter study in China.

BACKGROUND: Serum biomarkers have been widely adopted in clinical practice for assisting lung cancer diagnoses, therapeutic monitoring, and prognostication. The function of a well-performing tumor biomarker depends on a reliable reference interval (RI) with consideration of the study subjects' age, gender, and geographical location. This study aimed to establish a RI for each of 6 lung cancer biomarkers for use in the whole country of China on Mindray platform. METHODS: The levels of serum 6 lung cancer biomarkers-namely progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), and human epididymis protein 4 (HE4)-were measured utilizing the chemiluminescence immunoassay on the Mindray CL-6000i platform following the laboratory standard operating procedures in apparently healthy Chinese individuals on large cohort, multicenter, and geographical consideration bases. The CLSI EP28-A3C guideline was followed for the enrollment of study subjects. RESULTS: The age-stratified, gender-specific RIs for ProGRP, NSE, SCC, CEA, CYFRA21-1, and HE4 lung cancer biomarkers in the Chinese population have been established as described in the results and discussion in this work. In addition, various levels of the six lung cancer biomarkers among nine geographical locations in China have been observed. CONCLUSIONS: The sample volume of study cohort, age, and geographical location should be considered upon establishing a reliable biomarker RI. A RI for each of six lung cancer biomarkers has been established. The results from this study would be helpful for clinical laboratories in interpreting the analytical results and for clinicians in patient management.