Search Results (11)

Background/Objectives: The Vesical Imaging-Reporting and Data System (VI-RADS) provides high diagnostic accuracy for muscle-invasive bladder cancer; however, its prognostic value remains limited. We propose serum cytokeratin 19 fragment (CYFRA 21-1) and tumor contact length (TCL) as complementary prognostic factors. We aimed to construct a composite risk score integrating VI-RADS, CYFRA 21-1, and TCL for prognostic stratification. Methods: We retrospectively analyzed data from 101 patients with bladder cancer (BC) who underwent transurethral resection of bladder tumor (TURBT), magnetic resonance imaging, and postoperative serum CYFRA 21-1 measurement. For each factor, cut-off values were determined using receiver operating characteristic (ROC) analysis; meeting each threshold contributed one point (score range, 0–3). Overall survival (OS) was assessed using Kaplan–Meier and Cox regression analyses. Results: ROC analysis identified cut-offs of VI-RADS ≥ 3 (area under the curve [AUC] 0.779), TCL ≥ 40 mm (AUC 0.817), and CYFRA 21-1 ≥ 2.1 ng/mL (AUC 0.875). Based on these, patients were stratified into low- (0–1, n = 81), intermediate- (2, n = 12), and high-risk (3, n = 8) groups with 3-year OS rates of 95.1%, 75.0%, and 25.0%, respectively (p < 0.001). In univariate Cox regression, all factors significantly predicted poor OS: VI-RADS ≥ 3 (hazard ratio [HR], 6.51; p = 0.015), TCL ≥ 40 mm (HR, 8.36; p < 0.001), and CYFRA 21-1 ≥ 2.1 ng/mL (HR, 14.02; p < 0.001). In multivariate analysis, only CYFRA 21-1 remained independently significant (HR, 11.80; p < 0.001). Conclusions: A composite risk score combining VI-RADS, TCL, and CYFRA 21-1 effectively stratified patients with BC into distinct groups using minimally invasive, peri-TURBT assessments. Prospective multicenter validation is warranted. Full article

Background: Radon, a naturally occurring radioactive gas, is increasingly recognized as a major risk factor for lung cancer (LC), especially among non-smokers. The objective of this study was to identify serum biomarkers for the early detection of LC in individuals at high risk due to prolonged residential radon exposure in Chiang Mai, Thailand, and to assess whether the use of single or combined biomarkers improves the sensitivity and specificity of detection. Methods: A total of 15 LC patients and 30 healthy controls (HC) were enrolled. The HC group was further stratified into two subgroups: low radon (LR, n = 15) and high radon (HR, n = 15) exposure. All participants were non-smokers or former smokers. Serum levels of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor-alpha (TGF-alpha), and indoleamine 2,3-dioxygenase-1 (IDO-1) were measured using the Milliplex^® Kit on a Luminex^® Multiplexing Instrument (MAGPIX^® System). Results: Serum CEA, IL-6 and IL-8 levels were significantly higher in LC patients compared to the HC group (p < 0.05). Among analyzed biomarkers, only IL-8 was significantly elevated in LC patients compared to the HR group (p = 0.04). Notably, CYFRA 21-1 was the only biomarker that significantly differed between LR and HR groups (p = 0.004). The diagnostic potential of these biomarkers was evaluated using receiver operating characteristic (ROC) analysis. Individually, IL-6 showed the highest discriminative ability for differentiating LC patients from both HC and HR groups, with high specificity but moderate sensitivity. Combining IL-6 and IL-8 improved specificity and increased the area under the ROC curve (AUC), though it did not enhance sensitivity for distinguishing LC from HC. For distinguishing LC from HR individuals, IL-6 and CYFRA 21-1 exhibited strong diagnostic performance. Their combination significantly improved diagnostic accuracy, yielding the highest AUC, sensitivity, and specificity. In contrast, CEA, IL-8, TGF-alpha, and IDO-1 demonstrated limited diagnostic utility. Conclusions: Based on the available literature, this is the first study to evaluate the combined use of IL-6 and CYFRA 21-1 as potential biomarkers for LC screening in individuals with high residential radon exposure. Our findings highlight their utility, particularly in combination, for improving diagnostic accuracy in this high-risk population. Full article

The Vesical Imaging Reporting and Data System (VI-RADS) is used to detect muscle-invasive bladder cancer, with emerging prognostic implications. Integrating imaging parameters with molecular biomarkers may improve risk stratification in bladder cancer. This study evaluated whether combining VI-RADS scores with serum cytokeratin fragment 19 (CYFRA 21-1) levels—a clinically relevant biomarker for bladder cancer—could improve overall survival (OS) prediction. We retrospectively analyzed 134 patients who underwent transurethral resection of bladder tumors, magnetic resonance imaging, and postoperative serum CYFRA 21-1 measurements. In total, 15 cancer-specific deaths were observed during follow-up. Receiver operating characteristic curve analysis identified optimal prognostic cut-off values: VI-RADS score ≥ 4 and CYFRA 21-1 level ≥ 1.8 ng/mL. The 1-, 2-, and 3-year OS in patients with both high VI-RADS scores and CYFRA 21-1 levels were 42.9%, 16.7%, and 8.3%, respectively, significantly lower than those in other groups (p < 0.001, 0.002, and 0.003, respectively). Multivariate Cox proportional hazards analysis demonstrated that such patients had the poorest OS (hazard ratio: 7.51; p = 0.002). This suggests that combining VI-RADS and CYFRA 21-1 improves prognostic accuracy in bladder cancer, demonstrating potential clinical utility by informing individualized treatment strategies; however, limitations include the retrospective study design and absence of external validation. Full article

A novel approach to developing lateral flow assays (LFAs) for the detection of CYFRA 21-1 (cytokeratin 19 fragment, a molecular biomarker for epithelial-origin cancers) is proposed. Magnetic bioconjugates (MBCs) were employed in combination with advanced optical and magnetic tools to optimize assay conditions. The approach integrates such techniques as label-free spectral-phase interferometry, colorimetric detection, and ultrasensitive magnetometry using the magnetic particle quantification (MPQ) technique. For the first time in LFA applications, the MPQ-based and colorimetry-based detection methods were compared side by side, and superior analytical performance was demonstrated. The limit of detection (LOD) of 0.9 pg/mL was achieved using MPQ, and 2.9 pg/mL with optical detection. This study has demonstrated that MPQ provides elimination of signal saturation, higher sensitivity (slope of the calibration curve), and a 19-fold wider dynamic range of detected signals. Both optical and magnetic detection results are comparable to the best laboratory-based tests with the added benefits of a 20-min assay duration and the LFA format convenience. The assay effectiveness was validated in human serum and artificial saliva, and high recovery rates were observed. The proposed approach offers rapid and reliable detection of molecular biomarkers and holds significant potential for point-of-care diagnostics, particularly in resource-limited settings. Full article

Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and poses a significant public health challenge. Early detection is crucial for improving patient outcomes, with serum biomarkers such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCAg), and cytokeratin fragment 19 (CYFRA 21-1) playing a critical role in early screening and pathological classification of NSCLC. However, due to being mainly based on corresponding antibody binding reactions, existing detection technologies for these serum biomarkers have shortcomings such as complex operations, high false positive rates, and high costs. This study aimed to develop new methods for detecting CEA, SCCAg, and CYFRA 21-1 to assist in the diagnosis of NSCLC. Affinity peptides of CEA, SCCAg, and CYFRA 21-1, respectively, were screened by phage display technology, and the peptides’ binding affinities were determined by enzyme-linked immunosorbent assay and biolayer interferometry. Peptides with high affinity were then integrated as binding domains into biosensors by fusing them with circularly permuted fluorescent proteins (cpFPs) through genetic coding. The resulting biosensors, C4 biosensor for CEA, S1 biosensor for SCCAg, and Y3 biosensor for CYFRA 21-1, demonstrated robust sensitivity and specificity even at concentrations as low as 1 ng/mL for their respective tumor markers. When applied to clinical samples and recalibrated for the upper limit of normal concentrations, the biosensors exhibited enhanced sensitivity and specificity for NSCLC diagnosis. This study introduced innovative biosensors for the detection of CEA, SCCAg, and CYFRA 21-1, providing a highly sensitive, specific, rapid, and cost-effective diagnostic alternative that could significantly improve NSCLC screening rates. Full article

Current methods for the early diagnosis of cancer can be invasive and costly. In recent years, exosomes have been recognized as potential biomarkers for cancer diagnostics. The common methods for quantitative detection of exosomes, such as nanoparticle tracking analysis (NTA) and flow cytometry, rely on large-scale instruments and complex operation, with results not specific for cancer. Herein, we present a tri-channel electrochemical immunobiosensor for enzyme-free and label-free detecting carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragments (Cyfra21-1) from exosomes for specific early diagnosis of lung cancer. The electrochemical immunobiosensor showed good selectivity and stability. Under optimum experimental conditions, the linear ranges were from 10⁻³ to 10 ng/mL for CEA, 10⁻⁴ to 10² ng/mL for NSE, and 10⁻³ to 10² ng/mL for Cyfra21-1, and a detection limit down to 10⁻⁴ ng/mL was achieved. Furthermore, we performed exosome analysis in three kinds of lung cancer. The results showed a distinct expression level of exosomal markers in different types. These works provide insight into a promising alternative for the quantification of exosomal markers in specific diseases in the following clinical bioassays. Full article

Radon is a major cause of lung cancer (LC) deaths among non-smokers worldwide. However, no serum biomarker for screening of LC risk in high residential radon (HRR) areas is available. Therefore, the aim of this study was to determine diagnostic values of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), human epididymis protein 4 (HE4), interleukin 8 (IL-8), migration inhibitory factor (MIF), tumor nuclear factor-alpha (TNF-α) and vascular endothelial growth factors (VEGF) occurring in high radon areas. Seventy-five LC non-smoker patients and seventy-five healthy controls (HC) were enrolled in this study. Among the HC groups, twenty-five HC were low residential radon (LRR) and fifty HC were HRR. Significantly higher (p < 0.0004) serum levels of CEA, Cyfra21-1, IL-8 and VEGF were found in the LC compared with the LRR and HRR groups. More importantly, significantly higher levels (p < 0.009) of serum CEA, Cyfra21-1 and IL-8 were observed in HRR compared with the LRR group. Likewise, a ROC curve demonstrated that serum CEA and Cyfra21-1 could better distinguish LC risk from HRR groups than IL-8. These results indicated that serum CEA and Cyfra21-1 were significantly increased in the HRR group and may be considered as potential biomarkers for individuals at high-risk to develop LC. Full article

Background: This study investigated the impact of serum cytokeratin 19 fragment (CYFRA21-1) level on the clinical outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib (SOR) or lenvatinib (LEN). Methods: A total of 71 cases with unresectable HCC taking SOR or LEN were included. Univariate and multivariate analyses were performed to identify the prognostic factors in patients taking SOR or LEN. Results: Among the 71 patients taking SOR or LEN, the frequency of cases showing high CYFRA21-1 levels after administration increased compared to before the administration. There was no association between the CYFRA21-1 level and the result of treatment response using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 12 weeks after the administration. Univariate analysis identified a maximum intrahepatic tumor diameter of 70 mm or more, extrahepatic metastasis, baseline alpha-fetoprotein (AFP) ≥ 2000 ng/mL, baseline AFP-L3 index ≥ 15%, baseline des-gamma-carboxy prothrombin (DCP) ≥ 1000 mAU/mL, baseline CYFRA21-1 > 3.5 ng/mL, 12-week mRECIST progressive disease (PD), 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥ 2, administration period less than 12 weeks, ALBI grade 3 at PD, and no additional treatment after discontinuation of SOR/LEN as prognostic factors. Multivariate analysis revealed that AFP-L3 index ≥ 15%, 12-week mRECIST PD, 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥ 2, administration period less than 12 weeks, and no additional treatment after discontinuation of SOR/LEN were independent factors. Conclusions: Patients with a high CYFRA21-1 level at baseline tend to have poor prognosis, and patients with a high CYFRA21-1 ratio 12 weeks after administration have poor prognosis. Serum CYFRA21-1 measurement may have additional effects on prognostic prediction, and it may be necessary to pay close attention to the transition to the next HCC treatment in cases whose CYFRA21-1 level is high. Full article

Oral cancer poses a serious threat worldwide owing to its soaring case-fatality rate and its metastatic characteristics of spreading to the other parts of the body. Despite the recent breakthroughs in biomedical sciences, the detection of oral cancer at an early stage is still challenging. Conventional diagnosis in clinics and optical techniques to detect oral cancer in the initial stages are quite complicated as well as not completely accurate. To enhance the survival rate of oral cancer patients, it is important to investigate the novel methodologies that can provide faster, simpler, non-invasive, and yet ultraprecise detection of the onset of oral cancer. In this review, we demonstrate the promising aspects of an electrochemical biosensor as an ideal tool for oral cancer detection. We discuss the cutting-edge methodologies utilizing various electrochemical biosensors targeting the different kinds of biomarkers. In particular, we emphasize on electrochemical biosensors working at the molecular levels, which can be classified into mainly three types: DNA biosensors, RNA biosensors and protein biosensors according to the types of the analytes. Furthermore, we focus on the significant electrochemical methods including cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) to analyze the oral cancer biomarkers (such as IL-6, IL-8, CYFRA 21-1, CD 59 and CIP2A) present in body fluids including saliva and serum, using non-invasive manner. Hence, this review provides essential insights into the development of pioneering electrochemical biosensors for the detection of oral cancer at an early stage. Full article

Head and neck cancer (HNC) accounts for more than 330,000 cancer deaths annually worldwide. Despite late diagnosis being a major factor contributing to HNC mortality, no satisfactory biomarkers exist for early disease detection. Cytoplasmic gelsolin (cGSN) was discovered to predict disease progression in HNC and other malignancies, and circulating plasma gelsolin (pGSN) levels are significantly correlated with infectious and inflammatory disease prognoses. Here, the plasma levels of five candidate biomarkers (circulating pGSN, squamous cell carcinoma antigen, cytokeratin 19 fragment, soluble Fas, and soluble Fas ligand (sFasL)) in 202 patients with HNC and 45 healthy controls were measured using enzyme-linked immunosorbent assay or Millipore cancer multiplex assay. The results demonstrated that circulating pGSN levels were significantly lower in patients with HNC than in healthy controls. Moreover, circulating pGSN outperformed other candidate biomarkers as an independent diagnostic biomarker of HNC in both sensitivity (82.7%) and specificity (95.6%). Receiver operating characteristic curves indicated that combined pGSN and sFasL levels further augmented this sensitivity (90.6%) for early disease detection. Moreover, higher pGSN levels predicted improved prognosis at both 5-year overall survival and progression-free survival. In conclusion, circulating pGSN could be an independent predictor of favorable clinical outcomes and a novel biomarker for the early HNC detection in combination with sFasL. Full article

Introduction: The aim of the study was to assess the prognostic value of cytokeratin 19 fragments (Cyfra 21-1), carcinoembryonic antigen (CEA) and C-reactive protein (CRP) in surgically treated NSCLC patients. Material and Methods: 50 NSCLC patients (25 adenocarcinoma, 21 squamous cell and 4 adenosquamous), clinical stages I and II, age 42–89 years, entered the study. CEA, Cyfra 21-1 and CRP concentrations were measured in serum taken before surgery, CEA and Cyfra 21-1 in 50 patients, CRP—in 46 patients. The survival was calculated from the date of surgical treatment until death or until the end of the observation time. The results were expressed as medians (95%CI). Results: Cyfra 21-1 concentration was 2.1 (0.7–14.5) ng/mL. Survival time in the patients with Cyfra 21-1 ≤ 2 ng/mL, and > 2 ng/ /mL was 79 (14.85–88.2) and 29 (5.7–87.6) months, (p < 0.026). CEA concentration was 2.68 (0.87–72.7) ng/mL, significantly higher in adenocarcinoma than in squamous cell lung cancer — 4.38 ng/mL (1.67–41.35) vs. 2.2 ng/mL (1.0–6.1), p = 0.002. CRP concentration was 5.45 (0–122.6) mg/L. Significant dependence was found between CRP and pathological tumour size (pT). Median CRP values in pT1, pT2 and pT3+4 tumours were: 2.8 mg/L, 6.9 mg/L and 23.5 mg/L, respectively. Survival time of the patients with CRP ≤ 10 mg/L and CRP > 10 mg/L was 79 (14.85–88.2) and 29.5 (5.7–87.6) months, respectively (p = 0.045). CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only significant preoperative prognostic indicators (HR 2.08 and 2.04, respectively). Among the postoperative parameters, pathological stage of disease (p-stage) and pT were the significant prognostic indicators (HR 2.1 and 2.42, respectively). Conclusions: In the present study, concerning surgically treated NSCLC patients, preoperative CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only negative prognostic indicators, while pT and p-stage were significant postoperative prognostic indicators. Full article