• Korean Journal of Radiology
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• 제23권1호
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• pp.89-100
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• 2022

Objective: To improve the N biomarker in the amyloid/tau/neurodegeneration system by radiomics and study its value for predicting cognitive progression in individuals with mild cognitive impairment (MCI). Materials and Methods: A group of 147 healthy controls (HCs) (72 male; mean age ± standard deviation, 73.7 ± 6.3 years), 197 patients with MCI (114 male; 72.2 ± 7.1 years), and 128 patients with Alzheimer's disease (AD) (74 male; 73.7 ± 8.4 years) were included. Optimal A, T, and N biomarkers for discriminating HC and AD were selected using receiver operating characteristic (ROC) curve analysis. A radiomics model containing comprehensive information of the whole cerebral cortex and deep nuclei was established to create a new N biomarker. Cerebrospinal fluid (CSF) biomarkers were evaluated to determine the optimal A or T biomarkers. All MCI patients were followed up until AD conversion or for at least 60 months. The predictive value of A, T, and the radiomics-based N biomarker for cognitive progression of MCI to AD were analyzed using Kaplan-Meier estimates and the log-rank test. Results: The radiomics-based N biomarker showed an ROC curve area of 0.998 for discriminating between AD and HC. CSF Aβ42 and p-tau proteins were identified as the optimal A and T biomarkers, respectively. For MCI patients on the Alzheimer's continuum, isolated A+ was an indicator of cognitive stability, while abnormalities of T and N, separately or simultaneously, indicated a high risk of progression. For MCI patients with suspected non-Alzheimer's disease pathophysiology, isolated T+ indicated cognitive stability, while the appearance of the radiomics-based N+ indicated a high risk of progression to AD. Conclusion: We proposed a new radiomics-based improved N biomarker that could help identify patients with MCI who are at a higher risk for cognitive progression. In addition, we clarified the value of a single A/T/N biomarker for predicting the cognitive progression of MCI.

• KSBB Journal
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• 제26권4호
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• pp.352-356
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• 2011

The detection of biomarkers is an important issue for disease diagnosis. However, many systems are not suitable to detect the biomarker itself directly. For direct detection of biomarker proteins in human serum, a new affinity-capture method using aptamers combined with the mass spectrometry was suggested. Since signals from protein samples cannot be amplified, modified chromatin immunoprecipitation (ChIP) and subsequent cross-linking with formaldehyde between aptamers and target proteins were used not to lose the captured target proteins, which allowed us to perform a harsh washing step to remove the non-specifically bound proteins. As a model system, a thrombin aptamer was used as a bait and thrombin as a target protein. Using our modified ChIP and affinity-capture method, non-specific binding proteins on the beads decreased significantly, suggesting that our new method is efficient and can be applied to developing diagnosis systems for various biomarkers.

• 한국임상수의학회지
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• 제35권2호
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• pp.35-38
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• 2018

Recently assessment of suppression of tumorigenicity 2 (ST2) level has become a useful cardiac biomarker in human medicine. This study compared serum ST2 levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels between healthy dogs and dogs with chronic mitral valve disease. Twenty client-owned dogs were investigated. Dogs were divided into normal, asymptomatic, and symptomatic groups. Serum samples were used to measure levels of NT-proBNP and ST2. Samples for NT-proBNP were sent to IDEXX laboratory for analysis while ST2 levels were measured by using a canine interleukin 33 receptor ELISA kit. There was a significant difference in NT-proBNP levels between asymptomatic and symptomatic groups (P < 0.01), and between normal and symptomatic groups (P < 0.01). In contrast, ST2 levels were not relatively different between asymptomatic and symptomatic groups (P > 0.05). There was no significant difference was observed among all groups in ST2 study. The usefulness of measuring NT-proBNP level as a cardiac biomarker in dogs with chronic mitral valve disease was confirmed, but usefulness of the ST2 level was not observed. Further investigations are needed to evaluate the potential usefulness of ST2 level as a cardiac biomarker in canines.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6145-6149
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• 2012

Objective: To identify whether saliva supernatant miR-21 can serve as a novel potential biomarker in patients with esophageal cancer (EC). Methods: 32 patients with EC and 16 healthy controls were recruited in this study. Total RNA was extracted from saliva supernatant samples for measurement of miR-21 levels using RT-qPCR and relationships between miR-21 levels and clinical characteristics of EC patients were analyzed. Results: miR-21 was significantly higher in the EC than control groups. The sensitivity and specificity were 84.4% and 62.5% respectively. Supernatant miR-21 levels showed no significant correlation with cancer stage, differentiation and nodal metastasis. Conclusions: Saliva supernatant miR-21 may be a novel biomarker for EC.

• BMB Reports
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• 제41권9호
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• pp.626-634
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• 2008

Novel cancer biomarkers are required to achieve early diagnosis and optimized therapy for individual patients. Cancer is a disease of the genome, and tumor tissues are a rich source of cancer biomarkers as they contain the functional translation of the genome, namely the proteome. Investigation of the tumor tissue proteome allows the identification of proteomic signatures corresponding to clinico-pathological parameters, and individual proteins in such signatures will be good biomarker candidates. Tumor tissues are also a rich source for plasma biomarkers, because proteins released from tumor tissues may be more cancer specific than those from non-tumor cells. Two-dimensional difference gel electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye DIGE Fluor satulation dye) enables the efficient protein expression profiling of laser-microdissected tissue samples. The combined use of laser microdissection allows accurate proteomic profiling of specific cells in tumor tissues. To develop clinical applications using the identified biomarkers, collaboration between research scientists, clinicians and diagnostic companies is essential, particularly in the early phases of the biomarker development projects. The proteomics modalities currently available have the potential to lead to the development of clinical applications, and channeling the wealth of produced information towards concrete and specific clinical purposes is urgent.

• Mass Spectrometry Letters
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• 제1권1호
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• pp.21-24
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• 2010

The development of clinical biomarkers involves discovery, verification, and validation. Recently, multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (IDMS) has shown considerable promise for the direct quantification of proteins in clinical samples. In particular, multiple biomarkers have been tracked in a single experiment using MRM-based MS approaches combined with liquid chromatography. We report here a highly reproducible, quantitative, and dynamic MRM system for validating multi-biomarker proteins using Nanoflow HPLC-Microfluidics Chip/Triple-Quadrupole MS. In this system, transitions were acquired only during the retention window of each eluting peptide. Transitions with the highest MRM-MS intensities for the five target peptides from colon cancer biomarker candidates were automatically selected using Optimizer software. Relative to the corresponding non-dynamic system, the dynamic MRM provided significantly improved coefficients of variation in experiments with large numbers of transitions. Linear responses were obtained with concentrations ranging from fmol to pmol for five target peptides.

• BMB Reports
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• 제53권1호
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• pp.10-19
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• 2020

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis.

• Journal of Preventive Medicine and Public Health
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• 제42권6호
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• pp.343-348
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• 2009

The final decision of study design in molecular and genetic epidemiology is usually a compromise between the research study aims and a number of logistical and ethical barriers that may limit the feasibility of the study or the interpretation of results. Although biomarker measurements may improve exposure or disease assessments, it is necessary to address the possibility that biomarker measurement inserts additional sources of misclassification and confounding that may lead to inconsistencies across the research literature. Studies targeting multi-causal diseases and investigating gene-environment interactions must not only meet the needs of a traditional epidemiologic study but also the needs of the biomarker investigation. This paper is intended to highlight the major issues that need to be considered when developing an epidemiologic study utilizing biomarkers. These issues covers from molecular and genetic epidemiology (MGE) study designs including cross-sectional, cohort, case-control, clinical trials, nested case-control, and case-only studies to matching the study design to the MGE research goals. This review summarizes logistical barriers and the most common epidemiological study designs most relevant to MGE and describes the strengths and limitations of each approach in the context of common MGE research aims to meet specific MEG objectives.

• BMB Reports
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• 제57권3호
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• pp.155-160
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• 2024

Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment.

• Asian-Australasian Journal of Animal Sciences
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• 제31권7호
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• pp.1062-1071
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• 2018

The misuse of anabolic hormones or illegal drugs is a ubiquitous problem in animal husbandry and in food safety. The ban on growth promotants in food producing animals in the European Union is well controlled. However, application regimens that are difficult to detect persist, including newly designed anabolic drugs and complex hormone cocktails. Therefore identification of molecular endogenous biomarkers which are based on the physiological response after the illicit treatment has become a focus of detection methods. The analysis of the 'transcriptome' has been shown to have promise to discover the misuse of anabolic drugs, by indirect detection of their pharmacological action in organs or selected tissues. Various studies have measured gene expression changes after illegal drug or hormone application. So-called transcriptomic biomarkers were quantified at the mRNA and/or microRNA level by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technology or by more modern 'omics' and high throughput technologies including RNA-sequencing (RNA-Seq). With the addition of advanced bioinformatical approaches such as hierarchical clustering analysis or dynamic principal components analysis, a valid 'biomarker signature' can be established to discriminate between treated and untreated individuals. It has been shown in numerous animal and cell culture studies, that identification of treated animals is possible via our transcriptional biomarker approach. The high throughput sequencing approach is also capable of discovering new biomarker candidates and, in combination with quantitative RT-qPCR, validation and confirmation of biomarkers has been possible. These results from animal production and food safety studies demonstrate that analysis of the transcriptome has high potential as a new screening method using transcriptional 'biomarker signatures' based on the physiological response triggered by illegal substances.