Search Results (152)

Cholangiocarcinoma (CCA) in Northeast Thailand is characterized by late diagnosis and poor prognosis, creating a critical need for effective early-detection biomarkers. This study utilized a multi-omics approach to identify novel diagnostic targets and improve CCA screening. Initial serum proteomic and transcriptomic analyses revealed significant upregulation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in CCA patients, correlating with advanced disease stages. Interaction network analysis subsequently identified its circulating ligand, beta-human chorionic gonadotropin (β-hCG), as a highly translatable clinical target. The protein expression of β-hCG was assessed via immunohistochemistry (IHC) in 100 tissue samples, and serum levels of β-hCG, alongside routine markers (CA19-9, AFP, and CEA), were quantified in a cohort of 405 individuals, including 153 CCA patients. IHC confirmed significantly higher β-hCG expression in tumor tissues compared to adjacent areas (p < 0.0001). Serum β-hCG levels were significantly elevated in CCA patients and correlated with tumor volume and reduced overall survival. Diagnostically, a combined multiparameter panel (β-hCG, carbohydrate antigen 19-9, carcinoembryonic antigen, and alpha-fetoprotein) yielded excellent accuracy in distinguishing CCA from healthy controls (AUC: 0.962) and hepatocellular carcinoma cases (AUC: 0.890). However, discriminatory efficiency was notably lower when differentiating CCA from benign biliary diseases (AUC: 0.680) and liver metastases (AUC: 0.705). In conclusion, activation of the LHCGR signaling axis is a novel pathophysiological feature in CCA. When integrated into a multi-marker blood panel, circulating β-hCG serves as a valuable complementary risk-stratification and prognostic tool, though further optimization is required to overcome limited specificity in the presence of confounding liver pathologies before routine clinical implementation. Full article

Magnetic polymeric microspheres are pivotal solid-phase carriers in chemiluminescence enzyme immunoassays (CLEIA). However, their practical clinical application is frequently hindered by non-specific adsorption, irreversible aggregation, and the intrinsic susceptibility of exposed outermost Fe₃O₄ nanoparticles to oxidation. To overcome these critical bottlenecks, we rationally engineered highly original monodisperse P(St-MMA)@Fe₃O₄@P(St-MMA) sandwich-structured microspheres. The bespoke amphiphilic outer shell acts as an impenetrable shield against hydration and oxidation, while maintaining a topologically size-matched mesoporous network (average pore size of 13.11 nm) for optimal antibody anchoring. Strikingly, this architecture ensures exceptional long-term colloidal stability, completely preventing macroscopic agglomeration for over six months in buffer solutions. When evaluated in a carcinoembryonic antigen (CEA), CLEIA, our microspheres achieved an ultra-low limit of detection (LOD) of 0.055 ng·mL⁻¹ and high analytical recovery (93.37–108.25%). In a head-to-head comparison with industry-standard commercial magnetic beads, the engineered microspheres delivered stronger chemiluminescent signals and lower background noise, demonstrating excellent intra-assay (CV < 4.37%) and inter-assay (CV < 10%) precision. This work establishes a scalable, highly stable materials platform that effectively resolves the persistent oxidation limitations, holding immense practical importance for next-generation ultrasensitive clinical in vitro diagnostics. Full article

Background and Objectives: This study aimed to evaluate the diagnostic performance of endoscopic ultrasound (EUS) in comparison with computed tomography (CT) and magnetic resonance imaging (MRI) in the characterization of pancreatic lesions, and to assess the concordance of imaging findings with histopathological outcomes. Materials and Methods: A total of 76 patients who underwent EUS for pancreatic lesions between April 2021 and April 2022 were retrospectively analyzed. EUS findings were compared with CT and/or MRI in terms of lesion size, localization, and morphological characteristics. Histopathological results and laboratory parameters, including serum amylase, lipase, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9), were evaluated. Diagnostic performance metrics, including sensitivity, specificity, and accuracy, were calculated. Results: The study included 76 patients (55.3% male; mean age 59.93 ± 14.03 years). EUS demonstrated superior detection of lesions smaller than 2 cm (42.1% vs. 35.5%; p < 0.01) and a higher ability to identify solid components (17.1% vs. 9.7%; p < 0.01) compared to cross-sectional imaging. While overall sensitivity for malignancy was comparable between modalities, EUS showed higher specificity (58.33%) and diagnostic accuracy (55.26%). Pancreatic duct dilation, solid lesion morphology, larger lesion size, and elevated CA 19-9 levels were significantly associated with malignant pathology (p < 0.05). A descriptive agreement analysis revealed moderate concordance between EUS and radiological imaging in lesion size classification and morphological characterization. Conclusions: EUS demonstrates superior performance in detecting small pancreatic lesions and identifying solid components associated with malignancy. Although its sensitivity is comparable to CT and MRI, its higher specificity and diagnostic accuracy support its important role in lesion characterization. However, EUS should be considered complementary to cross-sectional imaging within a multimodal diagnostic approach. Integration of imaging findings with biochemical markers may further enhance diagnostic accuracy and clinical decision-making. Larger prospective studies with standardized protocols are warranted to validate these findings. Full article

Background: Gallbladder carcinoma (GBC) represents one of the most aggressive malignancies of the hepatobiliary system, evolving along a continuum from chronic inflammation to preneoplastic lesions and invasive cancer. This progression is frequently associated with gallstones and chronic cholecystitis and shares common pathogenic mechanisms with systemic inflammatory and metabolic disorders. Despite its relatively low incidence, GBC is characterized by poor prognosis, largely due to late-stage diagnosis and limited understanding of its molecular underpinnings. Methods: We conducted an observational study including 60 adult patients with radiologically suspected gallbladder cancer (GBC). Patients with disseminated disease, ongoing oncologic treatment, or synchronous malignancies were excluded. Fasting venous blood samples were collected to evaluate tumor markers and biochemical parameters, including carcinoembryonic antigen (CEA) and carbohydrate antigen CA 19-9. Surgical specimens were analyzed histopathologically and staged according to the European Society for Medical Oncology TNM classification system. Statistical analysis was performed using SPSS software (version 26.0), with appropriate parametric or non-parametric tests applied based on data distribution, and a p-value < 0.05 considered statistically significant. Results: Based on histological findings, patients were stratified into benign gallbladder disease (GBD) and GBC groups. CA 19-9 demonstrated higher mean serum levels with lower variability compared to CEA, suggesting superior sensitivity and diagnostic stability for gallbladder adenocarcinoma. In contrast, CEA levels exhibited greater fluctuation, limiting its reliability as a standalone biomarker. Importantly, the combined use of CA 19-9 and CEA improved diagnostic accuracy, supporting a multimarker approach for better clinical stratification. Our findings highlight the diagnostic value of CA 19-9 as a robust biomarker in GBC and support the integration of combined biomarker panels. Beyond tumor markers, the study identified a strong interplay between systemic inflammation and metabolic comorbidities, with obesity and hypertension significantly associated with chronic gallbladder pathology, and diabetes mellitus contributing to increased risk of acute inflammatory episodes. Elevated inflammatory markers, leukocytosis, and cholestatic enzyme alterations further supported the presence of a systemic inflammatory milieu. Multivariate analysis revealed that C-reactive protein (CRP), as a marker of systemic inflammation, was significantly influenced by a combination of clinical and biochemical variables, including age, hemoglobin, hypertension, amylase, CA 19-9, and CEA, explaining over 50% of its variability and up to 85% in advanced fibrotic changes. Additionally, platelet counts were significantly reduced in adenocarcinoma and correlated specifically with CA 19-9 levels, suggesting a potential link between tumor burden, inflammation, and platelet dynamics. Conclusions: Therefore, the observed associations between chronic inflammation, metabolic dysregulation, and tumor marker expression suggest a potential link between gallbladder carcinogenesis and systemic cardiometabolic pathways, opening new perspectives for early detection and targeted therapeutic strategies. Full article

Field-effect transistor (FET) biosensors using graphene have become one of the most promising biosensing platforms for the early diagnosis of diseases with features such as high sensitivity, label-free detection and application compatibility with point-of-care systems. Herein, we critically discuss recent advances in graphene FET (GFET) biosensor development toward clinically relevant biomarkers associated with representative diseases including cancer, neurodegenerative disease, infectious disease, and inflammatory conditions. Recent progress was reviewed to evaluate GFET architectures, surface functionalization methods, and detection quality. The biomarkers explored were clusterin in Alzheimer’s disease, thrombin in coagulopathy, estrogen receptor α (ER-α) in breast cancer, Carcinoembryonic antigen in lung cancer, microRNAs for malignant tumors, exosomes derived from HepG2 for the hepatocellular carcinoma (HCC) cell line, interleukin-6 (IL-6) for chronic obstructive pulmonary disease (COPD), Polyclonal antibodies and antigens (P24) for HIV and prostate-specific antigen for prostate cancer. The developed devices demonstrate ultralow detection limits at femtomolar to attomolar concentrations with the aid of designed antibodies, aptamers and nanomaterials. Herein, this review presents the sensing mechanisms and biomedical application of various GFET platforms, focusing on their emerging potential as next-generation platforms for rapid, non-invasive and point-of-care diagnostics. Full article

The availability of biobanked tissues represents an important resource for translational research; however, functional investigations are generally limited to freshly collected samples. To address this limitation, we developed an innovative strategy to restore functional properties of frozen biopsies by microtransplanting patient-derived membrane proteins into Xenopus laevis oocytes. This study aimed to recover and characterize the physiological properties of human colon cancer cell membranes and to investigate the role of neurotransmitter-related signaling and ion currents in cancer. Membrane incorporation was assessed by immunohistochemical detection of tumor-specific markers, including carcinoembryonic antigen, together with confocal microscopy and ultrastructural analyses. Functional viability was evaluated using two-electrode voltage clamp recordings to assess endogenous calcium-activated chloride currents and responses to selected neurotransmitters. The successful incorporation of colon cancer membranes was confirmed by specific immunoreactivity and ultrastructural features consistent with cancer cell architecture. Although no functional responses to the tested neurotransmitters were detected, oocytes microinjected with cancer membranes showed a marked reduction or complete suppression in endogenous calcium-activated chloride currents. These findings demonstrate that membrane microtransplantation into Xenopus oocytes is a reliable translational approach to functionally investigate cancer cell membranes from frozen biopsies, and suggest that altered chloride channel activity may represent a baseline for new studies to investigate new potential therapeutic targets for colon cancer. Full article

Objectives: In the absence of massive screening programs, it is imperative to develop and validate a candidate selection strategy for opportunistic endoscopic screening (OES) targeting the early detection of gastric cancer. Methods: A hospital-based cross-sectional study was conducted, enrolling both health check-up controls and gastric cancer patients. Data collection included two components: (1) a questionnaire including demography, self-reported comorbidities, and family history of cancers; (2) serology including hemoglobin, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Associations between potential variables and gastric cancer risk were assessed and the predictive efficacy of these risk factors was quantified. Sequentially, risk stratification scoring systems were constructed and their cost-effectiveness profiles were evaluated. Results: A total of 58,218 participants were included in the analysis, among whom 619 (1.1%) were gastric cancer patients. Multivariate analyses identified male, age >40 years, family history of gastric cancer, comorbidities of upper digestive tract benign diseases (UDTBDs), anemia, and elevated serum CEA and/or CA19-9 as independent risk factors of increasing gastric cancer risk. Cost-effectiveness analysis demonstrated that individuals, especially those symptomatic, presenting any of following conditions should be recommended for OES: (1) age ≥50 years, (2) family history of gastric cancer, and/or (3) comorbid UDTBDs. Elsewise, unclear anemia and/or elevated serum CEA and/or CA19-9 presenting among males and/or persons 41–50 years of age should be considered for OES. Notably, this selection strategy achieved a detection rate comparable to that of alternative protocols while yielding superior cost-effectiveness outcomes. Conclusions: The integrated strategy combining questionnaire and sequential serology represents an effective and cost-effective approach to identifying high-risk candidates for gastric cancer OES. Further investigations are warranted to develop more precise and tailored screening and surveillance protocols, with the aim of optimizing both detection rates and cost-effectiveness in clinical practice. Full article

Objectives: Pancreatic cystic lesions (PCLs) are increasingly detected due to the widespread use of imaging techniques. The identification of pancreatic mucinous cysts is especially important since these carry a risk of malignant transformation and require follow-up or surgical resection. The aim of this study was to determine the diagnostic yield of the molecular analysis of K-RAS (Kirsten RAt Sarcoma virus) and GNAS (Guanine Nucleotide-binding protein, Alpha Stimulating protein activity) gene mutations in pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA). Methods: In this prospective trial, we assessed the sensitivity, specificity, and positive and negative predictive values of K-RAS and GNAS mutation analysis in differentiating mucinous versus non-mucinous cysts and the subsequent impact on decision-making in daily clinical practice. The reference standard used comprised the combination of morphology on cross-sectional imaging and EUS, string sign, cyst fluid cytology, intracystic carcinoembryonic antigen (CEA), and glucose levels, with subsequent correlation of surgical pathology in resected cases. Fluid samples of 47 cysts obtained by EUS-FNA over a 39-month period were analyzed. Mutation analysis of KRAS (exon 2) was performed in all cases, and additionally, GNAS (exon 8) in 28 cases using Sanger sequencing. Results: 33 out of 47 PCLs were classified as mucinous cysts and 14 as non-mucinous cysts defined using conventional standards, including morphological characteristics, string-sign, cytology, cyst fluid testing, and histology in resected cases. Of these 33 mucinous cysts, KRAS mutation was detected in 14 samples. A further 23 mucinous lesions were additionally tested for GNAS mutation, which was detected in 10 of the 23 cysts. A 42.4% sensitivity for KRAS and 43.5% for GNAS mutation analysis was calculated, with a specificity of 92.9% and 100%, respectively, for detecting mucinous lesions. The clinical management was altered through the genetic testing results in one single case. Conclusions: In this cohort, K-RAS and GNAS mutational analysis in cyst fluid did not improve the detection of mucinous pancreatic cysts significantly after conventional testing. However, the method may be useful due to its high specificity in uncertain cases. Full article

The biomarker carcinoembryonic antigen (CEA) plays an important role in the diagnosis and monitoring of cancer, like breast, surveillance, colon, and liver cancer. The highly sensitive surface plasmon resonance (SPR) sensor presented in this work uses two-dimensional (2D) materials: BP/graphene, and the franckeite layer integrated in a Kretschmann configuration. The sensor structure, which includes a copper (Cu) layer and a CaF₂ prism, is intended to detect CEA in aqueous solutions with high accuracy. The proposed sensor’s performance was assessed using the transfer matrix method (TMM), with particular attention paid to important metrics like sensitivity, figure of merit (FoM), detection accuracy (DA), and penetration depth (PD). The proposed sensor achieved a sensitivity of 307.50 deg/RIU and a FoM of 61.62/RIU at a R_min value of 4.20 × 10⁻⁵ a.u. at a 40 nm Cu thickness, operating at a wavelength of 633 nm. The maximum sensitivity of 348.07 deg/RIU was achieved at 47 nm Cu thickness with BP layer, while the graphene layer yielded maximum sensitivity of 314.32 deg/RIU at the same Cu thickness. The results show that adding 2D layered materials to symmetric SPR sensors greatly improves detection performance, providing a promising foundation for the detection of clinical biomarkers in the future. Full article

Multiple-mode immunoassays have the advantages of self-correction, self-validation, and high accuracy and reliability. In this work, we developed a strategy for the design of triple-mode immunoassays with the self-assemblies of three-in-one small molecules as signal reporters. Pyrroloquinoline quinone (PQQ), with a well-defined redox peak and excellent spectroscopic and fluorescent signals, was chosen as the signaling molecule. PQQ was coordinated with Cu²⁺ to form metal–organic nanoparticle as the signal label. Hexahistidine (His₆)-tagged recognition element (recombinant streptavidin) was attached to the Cu-PQQ surface through metal coordination interaction between the His₆ tag and the unsaturated metal site. The captured Cu-PQQ nanoparticle released a large number of PQQ molecules under an acidic condition, which could be simultaneously monitoring by electrochemical, UV-vis, and fluorescent techniques, thereby allowing for the development of triple-model immunoassays. The three methods were used to determine the concentration of carcinoembryonic antigen (CEA) with the detection limits of 0.01, 0.1, and 0.1 ng/mL, respectively. This strategy opens up a universal route for the preparation of multiple-model signal labels and the oriented immobilization of bioreceptors for molecular recognition. Full article

Medullary thyroid carcinoma (MTC) is a thyroid tumor with neuroendocrine properties purportedly derived from C-cells. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryonic antigen, which are sensitive tumor markers, facilitating diagnosis, follow-up, and prognostication. Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterized by classic medullary thyroid carcinoma morphology without raised serum calcitonin and with or without the expression of calcitonin detected by immunohistochemistry. Previous studies reported that C-cells were derived from the neural crest; however, more recently, C-cells have been indisputably shown to be derived from the pharyngeal endoderm and ultimobranchial bodies. Ultimobranchial body (UBB) remnants can persist in the thyroid and express p63, but their function is poorly understood. Some have postulated that ultimobranchial bodies may be the “stem” cell of the thyroid and may be precursors for thyroid tumors, particularly mixed tumors with follicular and medullary components. We present a unique case of calcitonin-negative MTC in a 58-year-old male arising in an inflamed and fibrotic thyroid with numerous scattered ultimobranchial body remnants and concomitant C-cell hyperplasia/medullary microcarcinoma (CCH/MMC). The ultimobranchial body remnants, C-cell hyperplasia, and medullary thyroid carcinoma were MTC classifier positive according to ThyroSeq^®. The areas representing CCH/MMC expressed calcitonin by IHC while the main MTC tumor was negative. An additional unique feature was an area demonstrating a “mixed” C-cell/thyroid follicular epithelial phenotype. In this review we review the possible etiologies of calcitonin-negative MTC, the possibility of a neoplastic sequential progression from ultimobranchial bodies to CCH/MMC to medullary thyroid carcinoma with the individual elements (UBB, CCH/MMC, MTC) demonstrated in this thyroid, and previous postulations that ultimobranchial bodies may be the source of some follicular thyroid cancers, medullary thyroid cancers, and mixed tumors of medullary and follicular epithelial types. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. This study evaluates the predictive value of Carcinoembryonic Antigen (CEA) in identifying CRC recurrence following surgical resection. Methods: This retrospective study was realized in the Oncology Institute in Cluj-Napoca and included 88 patients diagnosed with CRC. Clinical, demographic, and tumor-specific data were collected, including TNM staging, tumor histology. CEA levels were recorded before surgery. Receiver Operating Characteristic (ROC) analysis was performed to determine the diagnostic accuracy of CEA in predicting tumor relapse, and the sensitivity and specificity of various CEA cut-off values were assessed. Results: Most patients presented with advanced-stage tumors (T3/T4, 80.6%). CEA levels were significantly higher in patients with lymphatic and perineural invasion and in those with metastases (mean CEA: 45.0 ng/mL for M1 vs. 13.2 ng/mL for M0, p = 0.032). ROC analysis revealed an area under the curve (AUC) of 0.877 (95% CI: 0.763–0.949). A CEA cut-off value of 11.73 ng/mL yielded 100% sensitivity and 74.5% specificity for detecting recurrence; Conclusions: CEA is a valuable non-invasive biomarker for predicting CRC relapse, with high sensitivity and acceptable specificity. Regular CEA monitoring post-surgery can facilitate early detection of recurrence, improving prognosis. Full article

This study presents a high-performance silicon nanowire (SiNW) array biosensor for the combined detection of two key colorectal cancer (CRC) biomarkers: circulating tumor DNA (ctDNA) and carcinoembryonic antigen (CEA). The device was fabricated using conventional micromachining techniques, enabling the integration of dual SiNW arrays on a single chip with precise control over structure and surface functionalization. Specific probe DNA and anti-CEA antibodies were immobilized on distinct array regions to facilitate targeted binding. The biosensor demonstrated exceptional performance, achieving an ultralow detection limit of 10 aM for ctDNA with a linear range from 0.1 fM to 10 pM, and a sensitivity of 1 fg/mL for CEA. It exhibited high selectivity against interfering substances, including single-base mismatched DNA and non-specific proteins, and maintained robust performance in human serum samples. The platform offers a scalable, label-free, and real-time detection solution with significant potential for application in early CRC screening and personalized medicine. Full article

Biliary tract diseases, including both benign and malignant conditions such as cholangitis, cholelithiasis, primary sclerosing cholangitis, cholangiocarcinoma, and gallbladder cancer, present significant challenges for timely diagnosis and effective clinical management. Conventional diagnostic approaches, which primarily rely on imaging and standard laboratory tests, often lack the sensitivity and specificity needed for early detection, accurate risk stratification, and personalized treatment planning. In recent years, advancements in point-of-care (POC) diagnostic technologies, along with the identification and validation of novel biomarkers, have begun to reshape the diagnostic landscape. This review provides a comprehensive overview of the clinical utility and limitations of current POC tests and biomarkers, ranging from well-established markers such as carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) to emerging molecular indicators such as circulating microRNAs and circulating tumor DNA. We examine their applications across acute management, chronic disease monitoring, and cancer detection; identify existing gaps in diagnostic practice; and discuss strategies for incorporating these tools into standard clinical workflows to enhance patient outcomes. Full article

Purpose: Near-infrared fluorescence-guided surgery (FGS) using cancer-specific tracers is promising for tailored gastric cancer (GC) surgery. Carcinoembryonic antigen (CEA) is a potential target due to its high expression in various digestive cancers, including GC. Materials and Methods: SGM-101, a chimeric anti-CEA monoclonal antibody conjugated with the near-infrared dye BM-104, was evaluated in GC. CEA expression was identified in GC cell lines at the mRNA and protein levels. Xenograft models (MKN-45, SNU-16, SNU-668, 85As2mLuc) were established in mice and injected with SGM-101 or PBS. Biodistribution was monitored using in vivo fluorescence imaging. Tumors were further analyzed by immunofluorescence. In a peritoneal carcinomatosis model, 85As2mLuc cells were injected intraperitoneally, and tumors were evaluated by bioluminescence and fluorescence and histology. Results: MKN-45, SNU-16, and 85As2mLuc were CEA-positive, while SNU-668 was CEA-negative. Flow cytometry confirmed CEA expression: MKN-45 (98%), SNU-16 (85.6%), SNU-668 (6.42%) and 85As2mLuc (78.4%). SGM-101 selectively targeted CEA-expressing tumors, with fluorescence peaking at 48 h, and immunofluorescence verified localization in tumor cells. In the peritoneal models, SGM-101 enabled precise detection of CEA-positive tumors. Conclusions: This study provides the first evidence for the feasibility of SGM-101 in gastric cancer, demonstrating its novelty and translational potential as a cancer-specific imaging agent for fluorescence-guided surgery. Full article