Topical Collection "Biomarkers in Medicine"

A topical collection in Diagnostics (ISSN 2075-4418). This collection belongs to the section "Pathology and Molecular Diagnostics".

Editors

Prof. Dr. Ludmilla Morozova-Roche
Website
Collection Editor
Department of Medical Biochemistry and Biophsyics, Umeå Univeristy, Umeå, SE 90187, Sweden
Interests: biodiagnostics; amyloid; protein misfolding; neuroinflammation; cellular toxicity; neurodegenerative diseases; blood serum; CSF; bioimaging
Dr. Cornelis F.M. Sier
Website SciProfiles
Collection Editor
Departments of Surgery and Gastroenterology, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands
Interests: biomarkers; cancer; metastasis; bone healing; angiogenesis; inflammation; cell–cell interactions; proteinases; growth factors; extracellular vesicles; diagnosis; prognosis; imaging; animal models

Topical Collection Information

Dear Colleagues,

The Topical Collection, "Biomarkers", will be focused on the diagnostics of a plethora of pathologies using biomarkers in the blood, cerebrospinal fluid (CSF), and other body fluids. These diseases include widely-spread ailments, such as cancer, diabetes, neurodegenerative Alzheimer’s, Parkinson’s, as well as other pathological conditions. Due to the growing elderly population, these diseases are on the rise in modern society and combatting them is a global issue. Early, or even pre-clinical, diagnostics of pathological conditions at the stage when the clinical symptoms are not yet obvious are of significant therapeutic value, and would enable administration of protective or preventive treatments. This may lead to a significant reduction in the social and healthcare costs of these diseases, as early diagnostics will culminate in more efficient treatment.

The molecular constitution of blood and other body fluids has been shown to be highly representative of the physiological state of an individual. Body-fluid specimen analyses (liquid biopsies) are minimally invasive and a relatively cheap means of early disease detection and convenient monitoring of disease response to therapeutic intervention. These approaches are tightly aligned with the concept of personalized healthcare. Over the last few years, a range of new biomarkers, associated with disease pathology, were discovered, and an arsenal of novel robust diagnostic assays for the (presymptomatic) detection of pathological conditions was established. Biodiagnostics is a rapidly expanding field, yet many questions and problems need to be solved. Some soluble candidate biomarkers failed to demonstrate clinical utility, which may be caused by insufficient association with the disease, or because their validation has been limited to a subset of patients, or by technical limitations in the detection methods.

The present Topical Collection aims at bringing primary research and review articles together to summarize state-of-the-art problems, solutions, and future directions in the biomarker and biodiagnostics field, based on the analysis of various body fluids. Your contribution is very welcome!

Prof. Dr. Ludmilla Morozova-Roche
Dr. Cornelis F.M. Sier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Ascites
  • Biomarkers
  • Biosensor assay
  • Diagnostics
  • Blood analysis
  • Cancer
  • Cerebrospinal fluid
  • Circulating tumor Cell
  • DNA, miRNA
  • Diabetes
  • Disease monitoring
  • Exosome
  • Liquid biopsy
  • Microvesicle
  • Neoplasia
  • Neurodegenerative disease
  • Metastasis
  • Plasma
  • Point of care device
  • Presymptomatic detection
  • Serum
  • Sputum
  • Tumor marker
  • Urine

Published Papers (15 papers)

2020

Jump to: 2019, 2018, 2017

Open AccessArticle
L1CAM, CA9, KLK6, HPN, and ALDH1A1 as Potential Serum Markers in Primary and Metastatic Colorectal Cancer Screening
Diagnostics 2020, 10(7), 444; https://doi.org/10.3390/diagnostics10070444 (registering DOI) - 30 Jun 2020
Abstract
Background: Colorectal cancer (CRC) screening at the earlier stages could effectively decrease CRC-related mortality and incidence; however, accurate screening strategies are still lacking. Considerable interest has been generated in the detection of less invasive tests requiring a small sample volume with the potential [...] Read more.
Background: Colorectal cancer (CRC) screening at the earlier stages could effectively decrease CRC-related mortality and incidence; however, accurate screening strategies are still lacking. Considerable interest has been generated in the detection of less invasive tests requiring a small sample volume with the potential to detect several cancer biomarkers simultaneously. Due to this, the ELISA-based method was undertaken in this study. Methods: Concentrations of neural cell adhesion molecule L1 (L1CAM), carbonic anhydrase IX (CA9), mesothelin (MSLN), midkine (MDK), hepsin (HPN), kallikrein 6 (KLK6), transglutaminase 2 (TGM2) aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), epithelial cell adhesion molecule (EpCAM), and cluster of differentiation 44 (CD44) from blood serum of 36 primary CRC and 24 metastatic CRC (mCRC) were calculated via MAGPIX® System (Luminex Corporation, USA). Results: Significantly increased concentration (p < 0.05) of three serum biomarkers (L1CAM, CA9, and HPN) were shown in mCRC when compared with primary CRC. HPN and KLK6 showed significant differences (p < 0.05) in concentration among different stages of CRC. In contrast, levels of HPN and ALDH1A1 were significantly elevated (p < 0.05) in chemotherapy-treated CRC patients as compared with nontreated ones. Conclusion: Serum biomarkers could act as a potential early CRC diagnostics test, but further additional testings are needed. Full article
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Open AccessArticle
KCTD15 Protein Expression in Peripheral Blood and Acute Myeloid Leukemia
Diagnostics 2020, 10(6), 371; https://doi.org/10.3390/diagnostics10060371 - 04 Jun 2020
Abstract
Leukocytes are major cellular components of the inflammatory and immune response systems. After their generation in the bone marrow from hematopoietic stem cells, they maturate as granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes. The abnormal accumulation and proliferation of immature blood cells [...] Read more.
Leukocytes are major cellular components of the inflammatory and immune response systems. After their generation in the bone marrow from hematopoietic stem cells, they maturate as granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes. The abnormal accumulation and proliferation of immature blood cells (blasts) lead to severe and widespread diseases such as leukemia. We have recently shown that KCTD15, a member of the potassium channel tetramerization domain containing protein family (KCTD), is remarkably upregulated in leukemic B-cells. Here, we extend our investigation by monitoring the KCTD15 expression levels in circulating lymphocytes, monocytes, and granulocytes, as well as in leukemia cells. Significant differences in the expression level of KCTD15 were detected in normal lymphocytes, monocytes, and granulocytes. Interestingly, we also found overexpression of the protein following leukemic transformation in the case of myeloid cell lineage. Indeed, KCTD15 was found to be upregulated in K562 and NB4 cells, as well as in HL-60 cell lines. This in vitro finding was corroborated by the analysis of KCTD15 mRNA of acute myeloid leukemia (AML) patients reported in the Microarray Innovations in Leukemia (MILE) dataset. Collectively, the present data open interesting perspectives for understanding the maturation process of leukocytes and for the diagnosis/therapy of acute leukemias. Full article
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Open AccessArticle
Biomarkers of Muscle Metabolism in Peripheral Artery Disease: A Dynamic NIRS-Assisted Study to Detect Adaptations Following Revascularization and Exercise Training
Diagnostics 2020, 10(5), 312; https://doi.org/10.3390/diagnostics10050312 - 16 May 2020
Abstract
We assessed whether muscle metabolism biomarkers (MMb) identified by near-infrared spectroscopy (NIRS) are valid for determining adaptations following revascularization or exercise training in peripheral artery disease (PAD). Eighteen patients (males n = 13; 69 ± 7 years) were randomized to receive revascularization (Rev [...] Read more.
We assessed whether muscle metabolism biomarkers (MMb) identified by near-infrared spectroscopy (NIRS) are valid for determining adaptations following revascularization or exercise training in peripheral artery disease (PAD). Eighteen patients (males n = 13; 69 ± 7 years) were randomized to receive revascularization (Rev = 6) or pain-free home-based exercise (Ex = 12). MMb were safely collected via a NIRS-assisted treadmill test as area-under-curve for the spectra of oxygenated (-oxy), deoxygenated (-deoxy), differential (-diff) and total (-tot) hemoglobin traces. MMb, ankle–brachial index (ABI), pain-free (PFWD) and 6-min (6MWD) walking distances were assessed at baseline and after four months. MMb were correlated at baseline with ABI (MMb-oxy r = 0.46) and 6MWD (MMb-tot r = 0.51). After treatments, MMb-oxy showed an expected increase, which was more relevant for Rev group than the Ex (56% vs. 20%), with trends towards normalization for the other MMb. These changes were significantly correlated with variations in ABI (MMb-oxy r = 0.71; p = 0.002) and 6MWD (MMb-tot r = 0.58; p = 0.003). The MMb-diff in Rev group and MMb-deoxy in Ex group at baseline predicted clinical outcomes being correlated with PFWD improvements after 4-month (r = −0.94; p = 0.005 and r = −0.57; p = 0.05, respectively). A noninvasive NIRS-based test, feasible in a clinical setting, identified muscle metabolism biomarkers in PAD. The novel MMb were associated with validated outcome measures, selectively modified after different interventions and able to predict long-term functional improvements after surgery or exercise training. Full article
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Open AccessReview
CCNE1 Amplification as a Predictive Biomarker of Chemotherapy Resistance in Epithelial Ovarian Cancer
Diagnostics 2020, 10(5), 279; https://doi.org/10.3390/diagnostics10050279 - 05 May 2020
Abstract
Ovarian cancer is the most-deadly gynecologic malignancy, with greater than 14,000 women expected to succumb to the disease this year in the United States alone. In the front-line setting, patients are treated with a platinum and taxane doublet. Although 40–60% of patients achieve [...] Read more.
Ovarian cancer is the most-deadly gynecologic malignancy, with greater than 14,000 women expected to succumb to the disease this year in the United States alone. In the front-line setting, patients are treated with a platinum and taxane doublet. Although 40–60% of patients achieve complete clinical response to first-line chemotherapy, 25% are inherently platinum-resistant or refractory with a median overall survival of about one year. More than 80% of women afflicted with ovarian cancer will recur. Many attempts have been made to understand the mechanism of platinum and taxane based chemotherapy resistance. However, despite decades of research, few predictive markers of chemotherapy resistance have been identified. Here, we review the current understanding of one of the most common genetic alterations in epithelial ovarian cancer, CCNE1 (cyclin E1) amplification, and its role as a potential predictive marker of cytotoxic chemotherapy resistance. CCNE1 amplification has been identified as a primary oncogenic driver in a subset of high grade serous ovarian cancer that have an unmet clinical need. Understanding the interplay between cyclin E1 amplification and other common ovarian cancer genetic alterations provides the basis for chemotherapeutic resistance in CCNE1 amplified disease. Exploration of the effect of cyclin E1 amplification on the cellular machinery that causes dysregulated proliferation in cancer cells has allowed investigators to explore promising targeted therapies that provide the basis for emerging clinical trials. Full article
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Open AccessArticle
Single Nucleotide and Copy-Number Variants in IL4 and IL13 Are Not Associated with Asthma Susceptibility or Inflammatory Markers: A Case-Control Study in a Mexican-Mestizo Population
Diagnostics 2020, 10(5), 273; https://doi.org/10.3390/diagnostics10050273 - 30 Apr 2020
Abstract
Background: Asthma is a complex and chronic inflammatory airway disease. Asthma’s etiology is unknown; however, genetic and environmental factors could affect disease susceptibility. We designed a case-control study aimed to evaluate the role of single-nucleotide polymorphisms (SNP), and copy-number variants (CNV) in the [...] Read more.
Background: Asthma is a complex and chronic inflammatory airway disease. Asthma’s etiology is unknown; however, genetic and environmental factors could affect disease susceptibility. We designed a case-control study aimed to evaluate the role of single-nucleotide polymorphisms (SNP), and copy-number variants (CNV) in the IL4 and IL13 genes in asthma susceptibility and their participation in plasma cytokine levels depending on genotypes Methods: We include 486 subjects, divided into asthma patients (AP, n = 141) and clinically healthy subjects (CHS, n = 345). We genotyped three SNP, two in the IL4 and two in the IL13 gene; also, two CNVs in IL4. The IL-4, IL-13 and IgE plasma levels were quantified. Results: Biomass-burning smoke exposure was higher in the AP group compared to CHS (47.5% vs. 20.9%; p < 0.01, OR = 3.4). No statistical differences were found in the genetic association analysis. In both CNV, we only found the common allele. For the analysis of IL-4, IL-13, and IgE measures stratified by genotypes, no significant association or correlation was found. Conclusion: In the Mexican-mestizo population, SNPs neither CNVs in IL4 nor IL13 are associated with asthma susceptibility or involved serum cytokine levels. Biomass-burning smoke is a risk factor in asthma susceptibility. Full article
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Open AccessArticle
miR-196B-5P and miR-200B-3P Are Differentially Expressed in Medulloblastomas of Adults and Children
Diagnostics 2020, 10(5), 265; https://doi.org/10.3390/diagnostics10050265 - 29 Apr 2020
Abstract
Medulloblastoma is a highly aggressive brain tumor that typically affects children, while in adults it represents ~1% of all brain tumors. Little is known about microRNA expression profile of the rare adult medulloblastoma. The main aim of this study was to identify peculiar [...] Read more.
Medulloblastoma is a highly aggressive brain tumor that typically affects children, while in adults it represents ~1% of all brain tumors. Little is known about microRNA expression profile of the rare adult medulloblastoma. The main aim of this study was to identify peculiar differences in microRNA expression between childhood and adult medulloblastoma. Medulloblastomas were profiled for microRNA expression using the Exiqon Human miRNome panel (I + II) analyzing 752 microRNAs in a training set of six adult and six childhood cases. Then, the most differentially expressed microRNAs were validated in a total of 21 adult and 19 childhood cases. Eight microRNAs (miR-196b-5p, miR-183-5p, miR-200b-3p, miR-196a-5p, miR-193a-3p, miR-29c-3p, miR-33b-5p, and miR-200a-3p) were differentially expressed in medulloblastoma of adults and children. Analysis of the validation set confirmed that miR-196b-5p and miR-200b-3p were significantly overexpressed in medulloblastoma of adults as compared with those of children. We followed an in silico approach to investigate direct targets and the pathways involved for the two microRNAs (miR-196b and miR-200b) differently expressed between adult and childhood medulloblastoma. Adult and childhood medulloblastoma have different miRNA expression profiles. In particular, the differential dysregulation of miR-196b-5p and miR-200b-3p characterizes the miRNA profile of adult medulloblastoma and suggests potential targets for novel diagnostic, prognostic, or therapeutic strategies. Full article
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Open AccessArticle
Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study
Diagnostics 2020, 10(4), 249; https://doi.org/10.3390/diagnostics10040249 - 23 Apr 2020
Abstract
We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in [...] Read more.
We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45−, and 4′,6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels. Full article
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Open AccessArticle
Serum Has Higher Proportion of Janus Kinase 2 V617F Mutation Compared to Paired EDTA-Whole Blood Sample: A Model for Somatic Mutation Quantification Using qPCR and the 2-∆∆Cq Method
Diagnostics 2020, 10(3), 153; https://doi.org/10.3390/diagnostics10030153 - 12 Mar 2020
Abstract
Detection of the Janus Kinase-2 (JAK2) V617F mutation is a diagnostic criterion for myeloproliferative neoplasms, and high levels of mutant alleles are associated with worse outcomes. This mutation is usually tested on blood DNA by allele-specific qPCR (AS-qPCR) and measured using absolute quantification. [...] Read more.
Detection of the Janus Kinase-2 (JAK2) V617F mutation is a diagnostic criterion for myeloproliferative neoplasms, and high levels of mutant alleles are associated with worse outcomes. This mutation is usually tested on blood DNA by allele-specific qPCR (AS-qPCR) and measured using absolute quantification. However, some automated DNA extractions co-extracts of PCR inhibitors from blood and qPCR absolute quantification need increased efforts in order to maintain standard curves. JAK2 V617F can also be detected in serum using droplet digital PCR (ddPCR), a specimen with less inhibitors and favorable to automated extractions, but ddPCR instruments are not wide available as qPCR thermocyclers. Here, we evaluate whether JAK2 V617F could be accurately quantified by AS-qPCR using the 2-∆∆Cq method on blood DNA and validate the assay using gold-standard molecular diagnostic protocols. Next, we apply the validated method to assess if the mutation could be reliably detected/quantified in serum. JAK2 V617F could be quantified by AS-qPCR using the 2-∆∆Cq method—the assay was highly accurate (bias of 1.91%) compared to a commercial kit, highly precise (total CV% of 0.40%, 1.92%, 11.12% for samples with 93%, 54%, and 2.5% of mutant allele), highly sensitive (limit of detection of 0.15%), and demonstrated a linear detection response from 1.1% to 99.9%. Serum presented a higher mutant allele burden compared to the paired whole blood (mean of 4%), which allows for an increased JAK2 mutant detection rate and favors increased JAK2 V617F high-throughput analysis. Full article
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Open AccessArticle
BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study
Diagnostics 2020, 10(2), 119; https://doi.org/10.3390/diagnostics10020119 - 21 Feb 2020
Abstract
Triple-negative breast cancer (TNBC) has several subtypes. The identification of markers associated with recurrence and poor prognosis in patients with TNBC is urgently needed. BRCAness is a set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation, or deletion, results in [...] Read more.
Triple-negative breast cancer (TNBC) has several subtypes. The identification of markers associated with recurrence and poor prognosis in patients with TNBC is urgently needed. BRCAness is a set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation, or deletion, results in DNA repair deficiency. In the current study, we evaluated the clinical significance and prognosis of BRCAness in a multicenter retrospective study. Ninety-four patients with TNBC treated with neoadjuvant chemotherapy were enrolled from three university hospitals for this retrospective study. BRCAness was evaluated in 94 core needle biopsy (CNB) specimens prior to neoadjuvant chemotherapy and 49 surgical specimens without pathological complete response (pCR). The samples were assessed using multiplex ligation-dependent probe amplification, and the amplicons were scored. Of the 94 patients, 51 had BRCAness in CNB specimens. There were no significant differences in pCR rates or recurrence between the BRCAness and non-BRCAness groups. Among surgical specimens, the BRCAness group had a significantly shorter recurrence-free survival and overall survival compared with the non-BRCAness group. The BRCAness of surgical specimens was found to be an important marker to predict prognosis in patients with TNBC after neoadjuvant chemotherapy. A clinical trial to assess the clinical impact of carboplatin with BRCAness is planned. Full article
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Open AccessReview
Diagnostic, Prognostic, and Therapeutic Value of Non-Coding RNA Expression Profiles in Renal Transplantation
Diagnostics 2020, 10(2), 60; https://doi.org/10.3390/diagnostics10020060 - 22 Jan 2020
Cited by 1
Abstract
End-stage renal disease is a public health problem responsible for millions of deaths worldwide each year. Although transplantation is the preferred treatment for patients in need of renal replacement therapy, long-term allograft survival remains challenging. Advances in high-throughput methods for large-scale molecular data [...] Read more.
End-stage renal disease is a public health problem responsible for millions of deaths worldwide each year. Although transplantation is the preferred treatment for patients in need of renal replacement therapy, long-term allograft survival remains challenging. Advances in high-throughput methods for large-scale molecular data generation and computational analysis are promising to overcome the current limitations posed by conventional diagnostic and disease classifications post-transplantation. Non-coding RNAs (ncRNAs) are RNA molecules that, despite lacking protein-coding potential, are essential in the regulation of epigenetic, transcriptional, and post-translational mechanisms involved in both health and disease. A large body of evidence suggests that ncRNAs can act as biomarkers of renal injury and graft loss after transplantation. Hence, the focus of this review is to discuss the existing molecular signatures of non-coding transcripts and their value to improve diagnosis, predict the risk of rejection, and guide therapeutic choices post-transplantation. Full article
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2019

Jump to: 2020, 2018, 2017

Open AccessArticle
Phospholipids are A Potentially Important Source of Tissue Biomarkers for Hepatocellular Carcinoma: Results of a Pilot Study Involving Targeted Metabolomics
Diagnostics 2019, 9(4), 167; https://doi.org/10.3390/diagnostics9040167 - 29 Oct 2019
Abstract
Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor [...] Read more.
Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue. Full article
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Open AccessArticle
The Effects of Low-Dose Irradiation on Human Saliva: A Surface-Enhanced Raman Spectroscopy Study
Diagnostics 2019, 9(3), 101; https://doi.org/10.3390/diagnostics9030101 - 22 Aug 2019
Cited by 1
Abstract
Biological effects of low-dose ionizing radiation (IR) have been unclear until now. Saliva, because of the ease of collection, could be valuable in studying low-dose IR effects by means of surface-enhanced Raman spectroscopy (SERS). The objective of our study was to compare the [...] Read more.
Biological effects of low-dose ionizing radiation (IR) have been unclear until now. Saliva, because of the ease of collection, could be valuable in studying low-dose IR effects by means of surface-enhanced Raman spectroscopy (SERS). The objective of our study was to compare the salivary SER spectra recorded before and after low-dose IR exposure in the case of pediatric patients (PP). Unstimulated saliva was collected from ten PP before and after irradiation with a cone beam computed tomography (CBCT) machine used for diagnostic purposes. The SERS measurements have been recorded on dried saliva samples using a solid nanosilver plasmonic substrate synthesized using an original method developed in our laboratory. The experimental results showed that salivary SER spectra are dominated by three vibrational bands (441,735 and 2107 cm−1) that can be assigned to bending and stretching vibrations of salivary thiocyanate (SCN-). After exposure, an immediate increase of vibrational bands assigned to SCN- has been recorded in the case of all samples, probably as a result of IR interaction with oral cavity. This finding suggests that SCN- could be used as a valuable biomarker for the detection and identification of low-dose radiation effects. Full article
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2018

Jump to: 2020, 2019, 2017

Open AccessArticle
Utility of Two-Dimensional Difference Gel Electrophoresis in Diagnosis of Multiple Sclerosis
Diagnostics 2018, 8(3), 44; https://doi.org/10.3390/diagnostics8030044 - 05 Jul 2018
Cited by 1
Abstract
Two-dimensional difference gel electrophoresis (2D-DIGE) has been used for identification of possible biomarkers in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, in different studies inconsistent results have been obtained. We wanted to analyze the diagnostic value of 2D-DIGE in early [...] Read more.
Two-dimensional difference gel electrophoresis (2D-DIGE) has been used for identification of possible biomarkers in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, in different studies inconsistent results have been obtained. We wanted to analyze the diagnostic value of 2D-DIGE in early MS patients by comparing protein patterns between single and pooled samples of MS patients and controls. CSF samples of 20 MS patients and 10 control subjects were processed with 2D-DIGE. The so obtained protein patterns were analyzed with DeCyder 6.5 software, whereby we described variation of patterns presented in one gel as well as between different gels. Even when running single samples of patients of the same group in one gel, variation of protein patterns was high. The number of identified spots with different protein level varied between 4 and 30, depending on which sample batches were compared. We did not find a consistent pattern throughout all possible batch combinations. The inter-individual variation of protein expression as well as the susceptibility of 2D-DIGE for methodological variations makes use of 2D-DIGE as a diagnostic tool for MS and for detection of possible candidate biomarkers difficult, since detected proteins vary depending on which samples are compared. Full article

2017

Jump to: 2020, 2019, 2018

Open AccessReview
Single Domain Antibodies as New Biomarker Detectors
Diagnostics 2017, 7(4), 52; https://doi.org/10.3390/diagnostics7040052 - 17 Oct 2017
Cited by 5
Abstract
Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition [...] Read more.
Biomarkers are defined as indicators of biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers have been widely used for early detection, prediction of response after treatment, and for monitoring the progression of diseases. Antibodies represent promising tools for recognition of biomarkers, and are widely deployed as analytical tools in clinical settings. For immunodiagnostics, antibodies are now exploited as binders for antigens of interest across a range of platforms. More recently, the discovery of antibody surface display and combinatorial chemistry techniques has allowed the exploration of new binders from a range of animals, for instance variable domains of new antigen receptors (VNAR) from shark and variable heavy chain domains (VHH) or nanobodies from camelids. These single domain antibodies (sdAbs) have some advantages over conventional murine immunoglobulin owing to the lack of a light chain, making them the smallest natural biomarker binders thus far identified. In this review, we will discuss several biomarkers used as a means to validate diseases progress. The potential functionality of modern singe domain antigen binders derived from phylogenetically early animals as new biomarker detectors for current diagnostic and research platforms development will be described. Full article
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Open AccessArticle
Comparison of Direct Sequencing, Real-Time PCR-High Resolution Melt (PCR-HRM) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) Analysis for Genotyping of Common Thiopurine Intolerant Variant Alleles NUDT15 c.415C>T and TPMT c.719A>G (TPMT*3C)
Diagnostics 2017, 7(2), 27; https://doi.org/10.3390/diagnostics7020027 - 12 May 2017
Cited by 5
Abstract
Thiopurine intolerance and treatment-related toxicity, such as fatal myelosuppression, is related to non-function genetic variants encoding thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G [...] Read more.
Thiopurine intolerance and treatment-related toxicity, such as fatal myelosuppression, is related to non-function genetic variants encoding thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G allele) in East Asians including Chinese can potentially prevent treatment-related complications. Two complementary genotyping approaches, real-time PCR-high resolution melt (PCR-HRM) and PCR-restriction fragment length morphism (PCR-RFLP) analysis were evaluated using conventional PCR and Sanger sequencing genotyping as the gold standard. Sixty patient samples were tested, revealing seven patients (11.7%) heterozygous for NUDT15 c.415C>T, one patient homozygous for the variant and one patient heterozygous for the TPMT*3C non-function allele. No patient was found to harbor both variants. In total, nine out of 60 (15%) patients tested had genotypic evidence of thiopurine intolerance, which may require dosage adjustment or alternative medication should they be started on azathioprine, mercaptopurine or thioguanine. The two newly developed assays were more efficient and showed complete concordance (60/60, 100%) compared to the Sanger sequencing results. Accurate and cost-effective genotyping assays by real-time PCR-HRM and PCR-RFLP for NUDT15 c.415C>T and TPMT*3C were successfully developed. Further studies may establish their roles in genotype-informed clinical decision-making in the prevention of morbidity and mortality due to thiopurine intolerance. Full article
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