scholarly journals Identification and Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Meng Li ◽  
Hongping Chen ◽  
Pengqi Yin ◽  
Jihe Song ◽  
Fangchao Jiang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Progression Free Survival ◽  
Extracellular Proteins ◽  
The Body ◽  
Clinical Samples ◽  
Ppi Network ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Potential Biomarkers

BackgroundMultiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoimmunity. No objective clinical indicators are available for the diagnosis and prognosis of MS. Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers. Our work will contribute to the in-depth study of the functions of extracellular proteins and the discovery of disease biomarkers.MethodsMS expression profiling data of the human brain was downloaded from the Gene Expression Omnibus (GEO). Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases. GO and KEGG were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the CSF of MS patients. ROC curve and survival analysis were used to evaluate the diagnostic and prognostic ability of key EP-DEGs.ResultsWe screened 133 EP-DEGs from DEGs. EP-DEGs were enriched in the collagen-containing extracellular matrix, signaling receptor activator activity, immune-related pathways, and PI3K-Akt signaling pathway. The PPI network of EP-DEGs had 85 nodes and 185 edges. We identified 4 key extracellular proteins IL17A, IL2, CD44, IGF1, and 16 extracellular proteins that interacted with IL17A. We clinically verified that IL17A levels decreased, but Del-1 and resolvinD1 levels increased. The diagnostic accuracy of Del-1 (AUC: 0.947) was superior to that of IgG (AUC: 0.740) with a sensitivity of 82.4% and a specificity of 100%. High Del-1 levels were significantly associated with better relapse-free and progression-free survival.ConclusionIL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS. We used bioinformatics methods to explore the biomarkers of MS and validated the results in clinical samples. The study provides a theoretical and experimental basis for revealing the pathogenesis of MS and improving the diagnosis and prognosis of MS.

scholarly journals Metabolomic Biomarkers of Multiple Sclerosis: A Systematic Review

2020 ◽  
Vol 7 ◽  
Author(s):  
Lachlan Porter ◽  
Alireza Shoushtarizadeh ◽  
George A. Jelinek ◽  
Chelsea R. Brown ◽  
Chai K. Lim ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
High Throughput Sequencing ◽  
Cochrane Library ◽  
Clinical Criteria ◽  
Diagnosis And Prognosis ◽  
Csf Analysis ◽  
Potential Biomarker ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Biomarkers

BackgroundMagnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and the McDonald’s clinical criteria are currently utilized tools in diagnosing multiple sclerosis. However, a more conclusive, consistent, and efficient way of diagnosing multiple sclerosis (MS) is yet to be discovered. A potential biomarker, discovered using advances in high-throughput sequencing such as nuclear magnetic resonance (NMR) spectroscopy and other “Omics”-based techniques, may make diagnosis and prognosis more reliable resulting in a more personalized and targeted treatment regime and improved outcomes. The aim of this review was to systematically search the literature for potential biomarkers from any bodily fluid that could consistently and accurately diagnose MS and/or indicate disease progression.MethodsA systematic literature review of EMBASE, PubMed (MEDLINE), The Cochrane Library, and CINAHL databases produced over a thousand potential studies. Inclusion criteria stated studies with potential biomarker outcomes for people with MS were to be included in the review. Studies were limited to those with human participants who had a clinically defined diagnosis of MS and published in English, with no limit placed on date of publication or the type of bodily fluid sampled.ResultsA total of 1,805 studies were recorded from the literature search. A total of 1,760 studies were removed based on their abstract, with a further 18 removed after considering the full text. A total of 30 studies were considered relevant and had their data retrieved and analyzed. Due to the heterogeneity of focus and results from the refined studies, a narrative synthesis was favored.ConclusionSeveral promising candidate biomarkers suitable for clinical application in MS have been studied. It is recommended follow-up studies with larger sample sizes be completed on several potential biomarkers.

Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9006-9006
Author(s):  
Joshua Bauml ◽  
Byoung Chul Cho ◽  
Keunchil Park ◽  
Ki Hyeong Lee ◽  
EUN KYUNG CHO ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Combination Regimen ◽  
Resistance Mutations ◽  
Tumor Biopsy ◽  
Potential Biomarker ◽  
Treatment Naïve ◽  
Exon 19 Deletion ◽  
Potential Biomarkers

9006 Background: Preliminary efficacy was observed with the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a 3rd-generation tyrosine kinase inhibitor, in both treatment-naïve and osimertinib (osi)-relapsed patients (pts) with EGFRm NSCLC (Cho Ann Oncol 2020;31:S813). We present updated results of the combination in osi-relapsed pts, including an analysis of potential biomarkers of response. Methods: Pts with EGFR exon 19 deletion or L858R mutation NSCLC, who had progressed on osi without intervening chemotherapy, were enrolled in the combination cohort of the ongoing CHRYSALIS study (NCT02609776). With pre-treatment tumor biopsies and ctDNA collected prospectively, pts received the combination dose of 1050/1400 mg amivantamab + 240 mg lazertinib to assess safety and efficacy in the osi-relapsed population. Response was assessed by investigator per RECIST v1.1. Osi-resistance mutations or amplifications in EGFR/MET identified by next-generation sequencing (NGS) in either ctDNA or tumor biopsy (biomarker-positive [pos]), were evaluated for enriching response. Immunohistochemistry (IHC) staining for EGFR and MET expression was also explored as a potential biomarker for response. Results: Of the 45 osi-relapsed pts, 36% (95% CI, 22–51) had a confirmed response (1 complete response and 15 partial responses [PR]). At a median follow-up of 8.2 mo (1.0–11.8), 20/45 pts (44%) remain on treatment. With 11/16 pts (69%) continuing in response (2.6–9.6+ mo), median duration of response has not been reached (NR). The median progression-free survival (mPFS) was 4.9 mo (95% CI, 3.7–8.3). In total, 44/45 pts were evaluable by ctDNA and 29/45 by tumor NGS. Genetic testing identified 17 biomarker-pos pts, of whom 8 (47%) responded. Of the remaining 28 pts, 8 (29%) responded. Among these 28 pts, 18 had unknown mechanisms of osi-resistance (8 PR) and 10 had non-EGFR/MET mechanisms of resistance identified (none responded). The mPFS (95% CI) for biomarker-pos and remaining pts was 6.7 mo (3.4–NR) and 4.1 mo (1.4–9.5), respectively. Adequate tissue was available for 20 pts to perform IHC testing for EGFR and MET–9/10 (90%) IHC high (combined EGFR+MET H score>400) pts responded to treatment, while 1/10 IHC low pts responded to treatment. Conclusions: Treatment with the combination of amivantamab and lazertinib yielded responses in 36% of chemotherapy-naïve pts who progressed on osi. Among these pts, genetic EGFR and MET-based biomarkers of resistance identified a subgroup of pts more likely to respond to amivantamab and lazertinib, although additional pts lacking identified resistance markers also responded. An IHC-based approach may identify pts most likely to benefit from the combination regimen, but further investigation is warranted. Clinical trial information: NCT02609776.

scholarly journals Molecular Docking Study on the Effect on Lamin –B1 through Compounds for the Treatment of Multiple Sclerosis

2021 ◽  
Vol 9 (VI) ◽  
pp. 5052-5057
Author(s):  
Sachin Verma
Keyword(s):  
Multiple Sclerosis ◽  
Molecular Docking ◽  
Demyelinating Disease ◽  
The Body ◽  
Computer Assisted ◽  
Ligand Molecule ◽  
Eye Muscle ◽  
Lamin B1 ◽  
Multiple Sclerosis Disease ◽  
Drug Designing

Multiple sclerosis (MS) is a demyelinating disease that can disrupt or damage various parts of our body i.e. nerve cells, brain and spinal cord, etc. The damaged cells of the body can disrupt the ability of the the nervous system to transmit signals for the functioning of the body. MS may result in double vision, blindness in one eye, muscle weakness and trouble with coordination and sensation. This disease is a long-term disease that may not be cured rapidly and easily. MS may be found at an age of 20-50. Lamin B1 is a protein that is found in humans. A gene i.e LMB1 encodes for this protein. The nuclear lamina consists of a 2D matrix of protein which locates next to the inner nuclear membrane. Molecular docking is a virtual or e tool that promotes the drug designing technique in a computerized way or called computer-assisted Drug Designing [CADD]. This can be used to complete the goal of docking is to see the binding of the protein and ligands In our study, one of the naturally occurring products was used for Multiple sclerosis treatment i.e Quercetin . The Quercetin ligand molecule gives a promising way of making the drug against the Multiple Sclerosis disease. According to this study, Quercetin may be used as a drug agent against Multiple Sclerosis disease in the future.

scholarly journals Case Report: Efficacy of Rituximab in a Patient With Familial Mediterranean Fever and Multiple Sclerosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Mattia Pozzato ◽  
Emanuele Micaglio ◽  
Chiara Starvaggi Cucuzza ◽  
Alessandro Cagol ◽  
Daniela Galimberti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Familial Mediterranean Fever ◽  
Demyelinating Disease ◽  
Cervical Spinal Cord ◽  
Mefv Gene ◽  
The Body ◽  
Drug Choice ◽  
Mediterranean Fever ◽  
The Right

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disease characterized by recurrent episodes of fever and serositis caused by mutations in the MEFV gene, while Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the CNS with genetic and environmental etiology. The two diseases rarely occur in association with relevant implications for clinical management and drug choice. In this paper, we present the case of a 53-year-old male with an autosomal dominant FMF since childhood who presented acute paresthesia at the right part of the body. He performed a brain and spinal cord MRI, which showed multiple brain lesions and a gd-enhancing lesion in the cervical spinal cord, and then received a diagnosis of MS. He then started Interferonβ-1a which was effective but not tolerated and caused hepatotoxicity, and then shifted to Rituximab with 3-month clinical and neuroradiological efficacy.

Circulating microRNAs as Potential Biomarkers in Glioma: A Mini Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Lavanya Choppavarapu ◽  
Sibin M. Kandi
Keyword(s):  
Glial Cells ◽  
Biological Fluids ◽  
Genetic Material ◽  
Micro Rna ◽  
Therapeutic Monitoring ◽  
Molecular Profile ◽  
Primary Glioblastoma ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Potential Biomarkers

: Glioma comprises of a group of heterogeneous brain tumors originating from glial cells. Primary glioblastoma are among the most common glial cells that have a characteristic clinical and molecular profile. Advancement in the field of cancer research and inventions of various clinical methodologies couldn’t improve the median survival of this deadly tumor from 12 months. The development of a non-invasive prognostic biomarker in blood would be a revolution in the diagnosis and therapeutic monitoring of this tumor. Extra cellular vesicles (Evs) are released from the tumor microenvironment into the blood, which contain the genetic material that represents the genetics of tumor cells. It is also seen that these Evs contain a variety of RNA population including miRNAs. Several studies identified that circulating cell free miRNAs, either free or present in Evs, could be considered as a potential biomarker in early diagnosis and prognosis of glioblastoma. Micro RNA studies in glioblastoma have found to be promising, as it reveals the biological pathway behind pathogenesis and helps in predicting the treatment targets. Literature says that various treatment methods change the type and quantity of miRNAs in biological fluids, which can be used to monitor the therapy. This review paper focuses on the role of circulating miRNAs as potential biomarkers in the diagnosis and clinical management of glioma patients.

scholarly journals MCM2 and NUSAP1 Are Potential Biomarkers for the Diagnosis and Prognosis of Pancreatic Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Yajun Deng ◽  
Hanyun Ma ◽  
Jinyong Hao ◽  
Qiqi Xie ◽  
Ruochen Zhao
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Diagnosis And Prognosis ◽  
Potential Biomarkers

Pancreatic cancer (PC) is one of the most malignant tumors. Despite considerable progress in the treatment of PC, the prognosis of patients with PC is poor. The aim of this study was to identify potential biomarkers for the diagnosis and prognosis of PC. First, the original data of three independent mRNA expression datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases and screened for differentially expressed genes (DEGs) using the R software. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the DEGs were performed, and a protein-protein interaction (PPI) network was constructed to screen for hub genes. The hub genes were analyzed for genetic variations, as well as for survival, prognostic, and diagnostic value, using the cBioPortal and Gene Expression Profiling Interactive Analysis (GEPIA) databases and the pROC package. After screening for potential biomarkers, the mRNA and protein levels of the biomarkers were verified at the tissue and cellular levels using the Cancer Cell Line Encyclopedia, GEPIA, and the Human Protein Atlas. As a result, a total of 248 DEGs were identified. The GO terms enriched in DEGs were related to the separation of mitotic sister chromatids and the binding of the spindle to the extracellular matrix. The enriched pathways were associated with focal adhesion, ECM-receptor interaction, and phosphatidylinositol 3-kinase (PI3K)/AKT signaling. The top 20 genes were selected from the PPI network as hub genes, and based on the analysis of multiple databases, MCM2 and NUSAP1 were identified as potential biomarkers for the diagnosis and prognosis of PC. In conclusion, our results show that MCM2 and NUSAP1 can be used as potential biomarkers for the diagnosis and prognosis of PC. The study also provides new insights into the underlying molecular mechanisms of PC.

scholarly journals Potential Biomarkers Associated with Multiple Sclerosis Pathology

2021 ◽  
Vol 22 (19) ◽  
pp. 10323
Author(s):  
Deepali Mathur ◽  
Bikash Kumar Mishra ◽  
Soumyashree Rout ◽  
Francisco Jose Lopez-Iranzo ◽  
Gerardo Lopez-Rodas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Immune Cells ◽  
Complex Disease ◽  
Response To Treatment ◽  
Imaging Biomarkers ◽  
Diagnosis And Prognosis ◽  
The Central Nervous System ◽  
Shed Light ◽  
Potential Biomarkers

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and promptly measured, their specificity, and their reproducibility. Biomarkers are classified into several categories depending on whether they address personal or predictive susceptibility, diagnosis, prognosis, disease activity, or response to treatment in different clinical courses of MS. The identified members indicate a variety of pathological processes of MS, such as neuroaxonal damage, gliosis, demyelination, progression of disability, and remyelination, among others. The present review analyzes biomarkers in cerebrospinal fluid (CSF) and blood serum, the most promising imaging biomarkers used in clinical practice. Furthermore, it aims to shed light on the criteria and challenges that a biomarker must face to be considered as a standard in daily clinical practice.

The miR-21 potential of serving as a biomarker for liver diseases in clinical practice

2020 ◽  
Vol 48 (5) ◽  
pp. 2295-2305
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Peng Gao ◽  
Rongxue Peng ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Liver Diseases ◽  
Hepatic Disease ◽  
Noninvasive Detection ◽  
Diagnosis And Prognosis ◽  
Expected Performance ◽  
Potential Biomarker ◽  
Disease Condition ◽  
Complex Regulatory Network

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.

Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis

2020 ◽  
Vol 19 (6) ◽  
pp. 376-385
Author(s):  
Md. A. Islam ◽  
Shoumik Kundu ◽  
Rosline Hassan
Keyword(s):  
Multiple Sclerosis ◽  
Gene Therapy ◽  
Disease Progression ◽  
Demyelinating Disease ◽  
Human Subjects ◽  
Mice Model ◽  
Focal Lesions ◽  
Protective Function ◽  
Monocytes And Macrophages ◽  
Specific Symptoms

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.

The SNPs within 3'UTR of miRNA Target Genes Related to Multiple Sclerosis: A Computational Prediction

2020 ◽  
Vol 17 (2) ◽  
pp. 133-147
Author(s):  
Mina Zafarpiran ◽  
Roya Sharifi ◽  
Zeinab Shirvani-Farsani
Keyword(s):  
Multiple Sclerosis ◽  
Gene Regulation ◽  
Binding Sites ◽  
Target Genes ◽  
Demyelinating Disease ◽  
Target Prediction ◽  
Computational Prediction ◽  
Functional Verification ◽  
Candidate Snps ◽  
Inflammatory Genes

Background: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system, and genetic factors play an important role in its susceptibility. The expressions of many inflammatory genes implicated in MS are regulated by microRNA (miRNAs), whose function is to suppress the translation by pairing with miRNA Recognition Elements (MREs) present in the 3' untranslated region (3'UTR) of target mRNA. Recently, it has been shown that the Single Nucleotide Polymorphism (SNPs) present within the 3'UTR of mRNAs can affect the miRNA-mediated gene regulation and susceptibility to a variety of human diseases. Objective: The aim of this study was to analyze the SNPs within the 3'UTR of miRNA inflammatory target genes related to multiple sclerosis. Methods: By DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases, 3'UTR genetic variants were identified in all inflammatory genes associated with MS. Also, miRNA's target prediction databases were used for predicting the miRNA binding sites. Results: We identified 125 SNPs with MAF>0.05 located in the binding site of the miRNA of 35 genes among 59 inflammatory genes related to MS. Bioinformatics analysis predicted 62 MRE-modulating SNPs and 59 MRE-creating SNPs in the 3'UTR of MSimplicated inflammatory genes. These candidate SNPs within miRNA binding sites of inflammatory genes can alter the miRNAs binding, and consequently lead to the mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in personalized medicine of MS, and hence, they would be valuable for further functional verification investigations.

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