Potential for trans-pulmonary tumor markers in the early diagnosis of lung cancer: a case report.

BACKGROUND: Measurement of tumor markers from peripheral venous blood is an emerging tool to assist in the early diagnosis of lung cancer. Samples from the pulmonary artery and pulmonary artery wedge position (trans-pulmonary samples) are accessible via right-heart catheterization and, by virtue of their proximity to lung tumors, may increase diagnostic yield. CASE PRESENTATION: We report a case of a 64 year-old woman from whom trans-pulmonary samples were obtained and who was diagnosed 16 months later with recurrent metastatic small cell lung cancer. Carcinoembryonic antigen, cytokeratin fragment 21 - 1 (CYFRA), and human epididymis protein 4 (HE4) levels demonstrated increasing concentrations across the pulmonary circulation. These gradients exceeded the assays' coefficient of variation by several-fold. For CYFRA and HE4, pulmonary artery wedge concentrations exceeded peripheral venous levels by more than 10% and peripheral arterial levels were up to 8% higher than peripheral venous levels. CONCLUSIONS: Evaluating the feasibility and utility of trans-pulmonary tumor markers for lung cancer diagnosis in a larger cohort should be considered. The addition of a peripheral arterial sample to standard peripheral venous samples may be a more practical alternative.

Simultaneous Detection of Collagen I Alpha II and Cytokeratin 19 mRNA by Multiplex qPCR in Liquid Biopsy in Diagnosis of Patients with Resectable Solid Tumors.

The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is essential. Accordingly, the objective of our work was to develop a non-invasive screening method for the early detection of various carcinomas in plasma using a panel that combines two markers using RT-qPCR. A retrospective case-control study was conducted to develop a cancer screening test based on the detection of stromal and epithelial biomarkers (COL1A2 and KRT19) in plasma. The expression of biomarkers was evaluated using multiplex quantitative PCR applied to 47 cases with non-metastatic tumors and 13 control participants. For both biomarkers, a cut-off value was stablished using Youden's J index through ROC curve analysis and areas under the curve (AUC) were calculated. The plasma mRNA expression level of both biomarkers was significantly higher in diseased versus healthy patients. Moreover, ROC curve analysis showed an AUC value of 0.897 for the combined model. This model also resulted in a cutoff value of 0.664, as well as a sensitivity of 83% and a specificity of 84.6%. These results suggest that the plasma expression levels of COL1A2 and KRT19 could a have potential role in detecting various types of cancer at the early stages. The combined analysis of both stromal and epithelial biomarkers would provide a non-invasive screening method that would allow us to differentiate patients with an active neoplastic process.

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OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR.

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

A sandwich-type photoelectrochemical biosensor based on anthocyanin-sensitized ZnO/P5FIn heterojunction for the sensitive detection of CYFRA21-1.

. A sandwich-type photoelectrochemical (PEC) immunosensor based on a ZnO/poly(5-formylindole) (P5FIn)/anthocyanin heterostructure was developed to achieve sensitive background-free detection of the tumor marker CYFRA21-1. ZnO with good photovoltaic properties is combined with narrow bandgap P5FIn to form a p-n type heterojunction. This structure reduces the electron-hole pair recombination, thereby enhancing the photocurrent response of the composite. Anthocyanidins are environmentally friendly natural compounds with excellent antioxidant, redox properties, and remarkable electrochemical activity. After sensitization by anthocyanins, the absorption and utilization of visible light in the composites are enhanced, further improving the PEC luminescence efficiency of the materials. Additionally, boron nitride quantum dots (BN QDs) are combined with Ab2 via polydopamine (PDA) as a secondary antibody marker, enhancing its sensitivity. The biosensor exhibited a linear detection range of 0.001-100 ng mL-1 with a limit of detection (LOD) of 0.00033 ng mL-1. Furthermore, this biosensor demonstrates excellent selectivity, reproducibility, and stability, as well as successful results in analyzing actual human serum samples. This approach provides a feasible method for tumor marker detection.

Application of computed tomography-based radiomics analysis combined with lung cancer serum tumor markers in the identification of lung squamous cell carcinoma and lung adenocarcinoma.

OBJECTIVE: To establish a prediction model of lung cancer classification by computed tomography (CT) radiomics with the serum tumor markers (STM) of lung cancer. MATERIALS AND METHODS: Two-hundred NSCLC patients were enrolled in our study. Clinical data including age, sex, and STM (squamous cell carcinoma [SCC], neuron-specific enolase [NSE], carcinoembryonic antigen [CEA], pro-gastrin-releasing peptide [PRO-GRP], and cytokeratin 19 fragment [cYFRA21-1]) were collected. A radiomics signature was generated from the training set using the least absolute shrinkage and selection operator (LASSO) algorithm. The risk factors were identified using multivariate logistic regression analysis, and a radiomics nomogram based on the radiomics signature and clinical features was constructed. The capability of the nomogram was evaluated using the training set and validated using the validation set. A correction curve and the Hosmer-Lemeshow test were used to evaluate the predictive performance of the radiomics model for the training and test sets. RESULTS: Twenty-nine of 1234 radiomics parameters were screened as important factors for establishing the radiomics model. The training (area under the curve [AUC] = 0.925; 95% confidence interval [CI]: 0.885-0.966) and validation sets (AUC = 0.921; 95% CI: 0.854-0.989) showed that the CT radiomics signature, combined with STM, accurately predicted lung squamous cell carcinoma and lung adenocarcinoma. Moreover, the logistic regression model showed good performance based on the Hosmer-Lemeshow test in the training (P = 0.954) and test sets (P = 0.340). Good calibration curve consistency also indicated the good performance of the nomogram. CONCLUSION: The combination of the CT radiomics signature and lung cancer STM performed well for the pathological classification of NSCLC. Compared with the radiomics signature method, the nomogram based on the radiomics signature and clinical factors had better performance for the differential diagnosis of NSCLC.

L-Cysteine functionalized magnetite nanoparticle adorned Ti3C2-MXene nanohybrid based screen printed immunosensor for oral cancer biomarker detection.

Nanohybrid based non-invasive biosensing platforms are emerging as promising alternatives to detect biomarkers in complex and diverse bio-fluids toward ultrasensitive point-of-care diagnostics. Herein, we report the development of a highly sensitive, facile, non-invasive, label free, affordable, and innovative electrochemical screen printed immunosensor for identifying CYFRA 21-1, an established and crucial biomarker for oral cancer. Until now, no work has been reported utilizing a titanium carbide Ti3C2 MXene nanosheet and L-cysteine (L-Cyst) functionalized magnetite nanoparticle (MNPs) nanohybrid based immunosensor for electrochemical detection of CYFRA 21-1. The L-Cyst@MNPs/Ti3C2-MXene nanohybrid was synthesized via the co-precipitation method and later deposited on a gold screen printed electrode (GSPE) offering enhanced surface area and electrochemical properties. The nanohybrid modified GSPE was then surface immobilized with monoclonal antibodies (anti-CYFRA-21-1) to fabricate an anti-CYFRA-21-1/L-Cyst@MNPs/Ti3C2-MXene/GSPE immunoelectrode and the non-specific locations of the immunoelectrode were covered with bovine serum albumin (BSA). The spectroscopic, morphological, and structural analyses of the synthesized nanohybrid and the fabricated electrodes were performed using different analytical techniques. The electrochemical studies of modified electrodes were evaluated using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The fabricated BSA/anti-CYFRA-21-1/L-Cyst@MNPs/Ti3C2-MXene/GSPE immunosensor has shown an excellent limit of detection of 0.023 ng mL-1, a linear detection range of (0.5-30) ng mL-1, a sensitivity of 277.28 µA (ng mL-1)-1 cm-2 and a lower limit of quantification of 0.618 ng mL-1 for electrochemical CYFRA 21-1 determination. Hence, this L-Cyst@MNPs/Ti3C2-MXene nanohybrid could also be explored as a potential candidate for determining other cancer biomarkers.

Sub-femtomolar vertical graphene field effect immunosensor for detection of lung tumor markers.

Lung cancer is the main cancer that endangers human life worldwide, with the highest mortality rate. The detection of lung tumor markers is of great significance for the early diagnosis and subsequent treatment of lung cancer. In this study, a vertical graphene field effect transistor (VGFET) immunosensor based on graphene/C60 heterojunction was created to offer quantitative detections for the lung tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), and neuron-specific enolase (NSE). The experimental results showed that the sensitive range for standard antigen is between 1 pg/ml to 100 ng/ml, with a limit of detection (LOD) of 5.6 amol/ml for CEA, 33.3 amol/ml for Cyfra 21-1 and 12.8 amol/ml for NSE (1 pg/ml for all). The detection accuracy for these tumor markers was compared with the clinically used method for clinical patients on serum samples. Results are highly consistent with clinically used immunoassay in its efficient diagnosis concentration range. Subsequently, the mesoporous silica nanospheres (MSNs) with an average size of 90 nm were surface modified with glutaraldehyde, and a second antibody was assembled on MSNs, which fixes nanospheres on the antigen and amplified the field effect. The LODs for three markers are 100 fg/ml (0.56 amol/ml for CEA) under optimal circumstances of detection. This result indicates that specific binding to MSNs enhances local field effects and can achieve higher sensing efficiency for tumor marker detection at extremely low concentrations, providing effective assistance for the early diagnosis of lung cancer.

The Diagnostic and Prognostic Value of the Combination of Tumor M2-Pyruvate Kinase, Carcinoembryonic Antigen, and Cytokeratin 19 Fragment in Non-Small Cell Lung Cancer.

Objective: Finding biomarkers related to non-small cell lung cancer (NSCLC) is helpful for the diagnosis and precise treatment of lung cancer. The relationship between serum tumor M2-pyruvate kinase (TuM2-PK), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment (CYFRA21-1) and NSCLC was analyzed. Methods: The serum levels of TuM2-PK, CEA, and CYFRA21-1 in 184 patients with the NSCLC group, 60 patients with the benign lung disease (BLD) group, and 90 healthy controls (HC) group were detected. The levels of TuM2-PK were measured by using an enzyme-linked immunosorbent assay. The detection methods of CEA and CYFRA21-1 were electrochemiluminescence. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of TuM2-PK, CEA, and CYFRA21-1 on NSCLC. The Kaplan-Meier survival curve was drawn to evaluate the survival status in NSCLC patients with different serum levels of TuM2-PK, CEA, and CYFRA21-1. Results: Serum levels of TuM2-PK, CEA, and CYFRA21-1 in the NSCLC group were significantly higher than those in the BLD group and the HC group (P < .01). Serum levels of TuM2-PK, CEA, and CYFRA21-1 in NSCLC patients were associated with the tumor lymph node metastasis stage (P < .05), lymph node metastasis (P < .05), and distant metastasis (P < .05). The ROC curve showed that the area under the curve of serum levels of TuM2-PK, CEA, and CYFRA21-1 was 0.814, 0.638, and 0.719, respectively, and that the combination of the above 3 was 0.918. The Kaplan-Meier survival curve showed that the 1-, 3- and 5-year survival rate in NSCLC patients with positive TuM2-PK, CEA, and CYFRA21-1 was significantly lower than that in NSCLC patients with negative TuM2-PK, CEA, and CYFRA21-1, respectively (P < .05). Conclusions: Serum TuM2-PK, CEA, and CYFRA21-1 levels have high clinical values in the diagnosis of NSCLC, and can effectively judge the prognosis of patients.

Dual-responsive electrochemical immunosensor for CYFRA21-1 detection based on Au/Co Co-loaded 3D ordered macroporous carbon interconnected framework.

Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a protein fragment released into the bloodstream during the death of lung epithelial cells, serving as a predictive biomarker in diagnosing non-small cell lung cancer (NSCLC) and need to be accurately detected. Herein, a dual-responsive label-free electrochemical immunosensor was developed based on a three-dimensional ordered interconnecting macroporous carbon skeleton material modified with gold-cobalt nanoparticles (Au/Co NPs-3D MCF) to detect cytokeratin-19 fragment (CYFRA21-1). The three-dimensional ordered interconnect macroporous structure, by providing a high specific surface area and an electrochemically active area, not only enhances the electron transport channel and reduces mass transfer resistance, but also offers a confined region that elevates the collision frequency with the active site. In addition to exhibiting excellent biocompatibility for antibody binding, gold-cobalt nanoparticles contribute significantly to the overall robustness of the immunosensor. By capitalizing on the 3D network structure and collective effect of Au and Co NPs, the Au/Co NPs-3D MCF immunosensors exhibit exceptional response signals in both chronocurrent testing and square-wave voltammetry, allowing for a wide linear response range of 0.0001-100 ng/mL and a low detection limit. Moreover, the constructed immunosensor is capable of detecting CYFRA21-1 in human serum and has the potential for further extension to detect multiple biomarkers. This work opens up new avenues for the construction of other highly selective 3D network immunosensors.

Large-scale proteomics reveals precise biomarkers for detection of ovarian cancer in symptomatic women.

Ovarian cancer is the 8th most common cancer among women and has a 5-year survival of only 30-50%. While the survival is close to 90% for stage I tumours it is only 20% for stage IV. Current biomarkers are not sensitive nor specific enough, and novel biomarkers are urgently needed. We used the Explore PEA technology for large-scale analysis of 2943 plasma proteins to search for new biomarkers using two independent clinical cohorts. The discovery analysis using the first cohort identified 296 proteins that had significantly different levels in malign tumours as compared to benign and for 269 (91%) of these, the association was replicated in the second cohort. Multivariate modelling, including all proteins independent of their association in the univariate analysis, identified a model for separating benign conditions from malign tumours (stage I-IV) consisting of three proteins; WFDC2, KRT19 and RBFOX3. This model achieved an AUC of 0.92 in the replication cohort and a sensitivity and specificity of 0.93 and 0.77 at a cut-off developed in the discovery cohort. There was no statistical difference of the performance in the replication cohort compared to the discovery cohort. WFDC2 and KRT19 have previously been associated with ovarian cancer but RBFOX3 has not previously been identified as a potential biomarker. Our results demonstrate the ability of using high-throughput precision proteomics for identification of novel plasma protein biomarker for ovarian cancer detection.

Evaluation of Serum Cytokeratines, Thymidine Kinase, and Growth Factors as Cancer Biomarkers in Colorectal Cancer.

BACKGROUND/AIM: Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis. PATIENTS AND METHODS: This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival. RESULTS: Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413. CONCLUSION: The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.

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.

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.

Diagnostic potential of protein serum biomarkers for distinguishing small and non-small cell lung cancer in patients with suspicious lung lesions.

BACKGROUND: Biomarkers play a role in identifying, managing, and predicting cancer outcomes. In lung cancer, they are used at various time points. Doubts remain regarding their accuracy for differential diagnosis and histological subtyping. A diagnostic test study was conducted. It included malignant lesions and controls with benign lesions. Before lung biopsy, all patients had the following biomarkers measured in serum (Pro-GRP,NSE,CYFRA21-1,SCC-Ag,CEA). METHODS: The predictive capacity of serum biomarkers was evaluated to discriminate between lung cancer and benign pathology. The accuracy was also assessed for distinguishing between SCLC and NSCLC and explored their ability to perform histological subtyping. RESULTS: 93 patients were included, 60 with lung cancer, 33 with benign pathology. Pro-GRP and NSE were elevated in SCLC compared with NSCLC or nonmalignant disease. The most accurate for differentiating between malignant and benign pathology were CEA and CYFRA21-1. Pro-GRP had a poor predictive capacity for distinguishing NSCLC from SCLC. However, combined with CEA and CYFRA21-1, performance improved. For SCLC, the diagnostic capacity of Pro-GRP increased by combining with biomarkers, such as NSE/CYFRA21-1. CONCLUSIONS: Biomarkers lacked the sensitivity and specificity for independent differential diagnosis or histological subtyping. However, the observed patterns in biomarker levels associated with specific histological subtypes suggest potential utility in a multi-biomarker approach or in conjunction with other diagnostic tools. This insight could guide future research to improve diagnostic accuracy and personalized treatment strategies in lung cancer.

Biomarkers are crucial for identifying, managing, and predicting outcomes in lung cancer, though they lack accuracy in differentiating histological subtypes.CEA and CYFRA21-1 were the most accurate biomarkers for distinguishing between malignant and benign pathology.Pro-GRP and NSE levels were elevated in SCLC compared to NSCLC. Pro-GRP alone had poor predictive capacity for differentiating NSCLC from SCLC, but combining it with CEA and CYFRA21-1 improved diagnostic performance.Patterns in biomarker levels suggest that a multi-biomarker approach, especially when combined with other diagnostic tools, could improve diagnostic accuracy.

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.

Use of tumor markers in distinguishing lung adenocarcinoma-associated malignant pleural effusion from tuberculous pleural effusion.

BACKGROUND: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis. METHODS: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables. RESULTS: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1. CONCLUSIONS: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained.

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.