Marker For Diagnosis Of Disease Research Articles

Role of long noncoding RNAs in malignant disease (Review)

Long noncoding RNAs (lncRNAs) are endogenous transcribed RNA molecules without protein-coding potential, ranging between 200 and 100,000 nt in length. LncRNAs regulate the expression of specific genes in several ways, including guiding chromatin-remodeling, and affecting splicing, transcription or translation. The mutations and dysregulation of lncRNAs have been found to be important in various human diseases, but particularly in human cancer. Previous studies have demonstrated that changes to lncRNAs are closely associated with tumorigenesis, metastasis, prognosis and diagnosis. The current review aims to present a brief overview of the associated reports of lncRNAs in malignant neoplasms, including breast cancer, prostate cancer and hematological malignancies. LncRNAs may be evaluated as novel markers in disease diagnosis, and as prospective therapeutic targets for the prevention and treatment of human diseases.

Single nucleotide polymorphism in the SEPS1 gene may contribute to the risk of various human diseases: a meta-analysis

Background: Recently the G-105A promoter polymorphism in SEPS1 has been shown to increase pro-inflammatory cytokine expression and, thus, to be correlated with various types of human cancers and diseases.Aims: This study examined whether this functional polymorphism was related to the risks of several human diseases by performing a meta-analysis.Subjects and methods: This study identified all published studies in MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, Current Contents Index and three Chinese databases.Results and conclusions: Eleven case-control studies were incorporated into this meta-analysis. The results showed that carriers of the rs28665122 G > A polymorphism in the SEPS1 gene are at increased risk of developing diseases under five genetic models. According to the ethnicity-stratified sub-group analysis, SEPS1 rs28665122 polymorphism is significantly linked to increased risk of developing related diseases in Europeans under five genetic models; but not among Asians. This data indicates a statistical association between SEPS1 rs28665122 G > A variants and the development of various human diseases. Such findings suggest that SEPS1 may be a potential gene marker for disease diagnosis and prognosis.

Near infrared Raman spectroscopic characterization of blood plasma of normal, oral premalignant and malignant conditions—a pilot study

The metabolic end products from cells/tissues that are released into the circulating blood stream and any changes in their level because of pathological conditions may be used as markers in disease diagnosis. Raman spectroscopy has been exploited to characterize the biomolecules present in the blood plasma of clinically confirmed normal group, premalignant (Oral Sub Mucous Fibrosis) and malignant (Oral Squamous Cell Carcinoma) at 784.15 nm. Raman spectral signatures show relatively less intense Raman bands of phenylalanine, lipid and antioxidant beta carotene but higher intense bands for proteins, DNA base components and amino acids (tyrosine and tryptophan) for malignant group than that of normal group. However premalignant group possess high intense Raman bands for amino acids (tyrosine and tryptophan) at 830, 1020 and 1620 cm−1 and protein peaks at 913, 978 and 1646 cm−1 when compared to that of malignant and normal group. Principal component analysis coupled with linear discriminant analysis (PCA‐LDA) yielded a diagnostic sensitivity of 96.3% and 91.2%, and a specificity of 80.0% and 96.7% in the classification of normal from premalignant and normal from malignant, respectively. This indicates that Raman spectroscopy of blood plasma has the potential in classifying normal and oral malignancy conditions. Copyright © 2015 John Wiley & Sons, Ltd.

Calreticulin and JAK2V617F Mutations in Essential Thrombocythemia and Their Potential Role in Diagnosis and Prognosis

Mutation in calreticulin (CALR) has been recently detected in essential thrombocythemia (ET) patients lacking JAK2V617F mutation. The absence of JAK2V617F mutation in 50% of patients with ET has indicated the importance of new markers for disease diagnosis, including CALR. Considering the detection of CALR in these patients, in this paper we study the structure and function of CALR protein and JAK2V617F as well as their diagnostic and prognostic role in ET patients.

Low Frequency of Pendrin Autoantibodies Detected Using a Radioligand Binding Assay in Patients With Autoimmune Thyroid Disease

Pendrin is a transmembrane protein located at the apical end of the thyrocyte in which it mediates the efflux of iodide through the thyroid follicular cell. Recently pendrin was described as a significant antibody target in Japanese patients with Graves' disease (GD) or autoimmune hypothyroidism (AH) using an immunoblotting assay. However, a subsequent study failed to verify this in autoimmune thyroid disease (ATD) patients of Tunisian origin. The aim of the current study was to evaluate a UK population of patients with ATD for the presence of pendrin autoantibodies using a novel radioligand binding assay (RBA). Sera from 71 GD and 66 AH patients and 28 healthy controls were evaluated for pendrin autoantibody reactivity in RBAs. The results indicated that 8.8% of patients with ATD (9.9% GD and 7.6% AH) were positive for pendrin autoantibodies. Overall, the frequency of pendrin autoantibodies did not differ significantly between the ATD patient cohorts and the healthy control group: P = .186 and P = .317 for GD and AH patients, respectively. Pendrin autoantibodies, detected using a novel RBA, are not widely prevalent in UK patients with ATD, nor do they differ in frequency between GD and AH. These autoantibodies are therefore unlikely to be a useful marker for disease diagnosis, although the role that pendrin may play as an autoantigen in the initiation or maintenance of thyroid autoimmunity remains to be established.

Identification of 129S6/SvEvTac-Specific Polymorphisms on Mouse Chromosome 11

Polymorphisms such as single-nucleotide polymorphisms (SNPs) and insertions/deletions (Indels) can be associated with phenotypic traits and be used as markers for disease diagnosis. Identification of these genetic variations within laboratory mice is crucial to improve our understanding of the genetic background of the mice used for research. As part of a positional cloning project, we sequenced six genes (Mettl16, Evi2a, Psmd11, Cct6d, Rffl, and Ap2b1) within a 6.8-Mb domain of mmu chr 11 in the C57BL/6J and 129S6/SvEvTac inbred strains. Although 129S6/SvEvTac is widely used in the mouse community, there is very little current (or projected future) sequence information available for this strain. We identified 6 Indels and 21 novel SNPs and confirmed genotype information for 114 additional SNPs in these 6 genes. Mettl16 and Ap2b1 contained the largest numbers of variants between the C57BL/6J and 129S6/SvEvTac strains. In addition, we found five new SNPs between 129S6/SvEvTac and 129S1/SvImJ within the Ap2b1 locus. Although we did not detect differences between C57BL/6J and 129S6/SvEvTac within Evi2a, this locus contains a relatively high SNP density compared with the surrounding sequence. Our study highlights the genetic differences among three inbred mouse strains (C57BL/6J, 129S6/SvEvTac, and 129S1/SvImJ) and provides valuable sequence information that can be used to track alleles in genomics-based studies.

AN UNUSUAL CASE OF LYMPHOCYTIC HYPOPHYSITIS IN AYOUNG MAN PRESENTING WITH ELEVATED SERUM IGF-1

Objective. To describe an unusual case of lymphocytic hypophysitis in a man, presenting with an elevated serum Insulin like growth factor-1(IGF-1) level. Case report. We report the case of a 27 year old male presenting with a 2 week history of severe headaches. Magnetic resonance imaging of the head showed an adenoma-like pituitary. The physical examination was normal, laboratory tests revealed secondary hypothyroidism and hypogonadism along with an elevated IGF-1. Complete transsphenoidal resection of the pituitary mass was done. Tissue analysis was diagnostic for lymphocytic hypophysitis. No evidence of a somatotroph adenoma was found. After surgery the patient developed panhypopituitarism and diabetes insipidus. Discussion. IGF-1 is a sensitive disease related marker in acromegaly and corresponds to disease activity. However, it should not be used as the sole marker for diagnosis of disease. Inflammatory lesions of the pituitary gland, such as lymphocytic hypophysitis, can clinically and radiologically mimic tumors of the sellar region. Conclusion. We report an index case of a young male who presented with elevated serum IGF-1 level in the setting of lymphocytic hypophysitis. This case illustrates the dilemma associated with reliance on the IGF-1 levels for diagnosis of acromegaly, since an elevated IGF-1 level in the presence of a pituitary mass may not always be a somatotroph tumor. We propose the differential diagnosis should also include autoimmune hypophysitis.

Gauging the Performance of SNPs, Biomarkers, and Clinical Factors for Predicting Risk of Breast Cancer

Gauging the Performance of SNPs, Biomarkers, and Clinical Factors for Predicting Risk of Breast Cancer

Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients

IntroductionMicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this study, the expression of selected microRNAs is examined in rheumatoid arthritis.MethodsTotal RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR.ResultsRheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals. In addition, two targets of miR-146a, namely tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK-1), were similarly expressed between rheumatoid arthritis patients and control individuals, despite increased expression of miR-146a in patients with rheumatoid arthritis. Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-α production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-α production.ConclusionsRecent studies have shown that synovial tissue and synovial fibroblasts from patients with rheumatoid arthritis exhibit increased expression of certain microRNAs. Our data thus demonstrate that microRNA expression in rheumatoid arthritis peripheral blood mononuclear cells mimics that of synovial tissue/fibroblasts. The increased microRNA expression in rheumatoid arthritis patients is potentially useful as a marker for disease diagnosis, progression, or treatment efficacy, but this will require confirmation using a large and well defined cohort. Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-α production in patients with rheumatoid arthritis.

Neuropeptidomics: expanding proteomics downwards

Biological function is mainly carried out by a dynamic population of proteins and peptides which may be used as markers for disease diagnosis, prognosis and as a guide for effective treatment. The study of proteins is called proteomics and it is generally performed by two-dimensional gel electrophoresis and mass spectrometric methods. However, gel-based proteomics is methodologically restricted from the low mass region, which includes important endogenous peptides. The study of endogenous peptides, peptidomics, is complicated by protein fragments produced post-mortem during conventional sample handling. Nanoflow liquid chromatography and MS, together with improved methods for sample preparation, have been used to semi-quantitatively monitor endogenous peptides in brain tissue. When rapidly heat-denatured brain tissue was analysed, these methods enabled simultaneous detection of hundreds of peptides and the identification of several endogenous peptides not previously described in the literature. In an application of the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model for Parkinson's disease, the expression of the small protein PEP-19 was compared with controls. The levels were found to be significantly decreased in the striatum of MPTP-treated animals.

The Role of Human HtrA1 in Arthritic Disease

Human HtrA1 belongs to a widely conserved family of serine proteases involved in various aspects of protein quality control and cell fate. Although HtrA1 has been implicated in the pathology of several diseases, its precise biological functions remain to be established. Through identification of potential HtrA1 targets, studies presented herein propose that within the context of arthritis pathology HtrA1 contributes to cartilage degradation. Elevated synovial HtrA1 levels were detected in fluids obtained from rheumatoid and osteoarthritis patients, with synovial fibroblasts identified as a major source of secreted HtrA1. Mass spectrometry analysis of potential HtrA1 substrates within synovial fluids identified fibronectin as a candidate target, and treatment of fibronectin with recombinant HtrA1 led to the generation of fibronectin-degradation products that may be involved in cartilage catabolism. Consistently, treatment of synovial fibroblasts with HtrA1 or HtrA1-generated fibronectin fragments resulted in the specific induction of matrix metalloprotease 1 and matrix metalloprotease 3 expression, suggesting that HtrA1 contributes to the destruction of extracellular matrix through both direct and indirect mechanisms.