Circulating microRNAs as Potential Biomarkers in Glioma: A Mini Review

Author(s):  
Lavanya Choppavarapu ◽  
Sibin M. Kandi

: 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.

2020 ◽  
Vol 7 ◽  
Author(s):  
Lachlan Porter ◽  
Alireza Shoushtarizadeh ◽  
George A. Jelinek ◽  
Chelsea R. Brown ◽  
Chai K. Lim ◽  
...  

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.


2019 ◽  
Vol 20 (13) ◽  
pp. 3148 ◽  
Author(s):  
Takashi Hosaka ◽  
Takenari Yamashita ◽  
Akira Tamaoka ◽  
Shin Kwak

Recent progress in the research for underlying mechanisms in neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) has led to the development of potentially effective treatment, and hence increased the need for useful biomarkers that may enable early diagnosis and therapeutic monitoring. The deposition of abnormal proteins is a pathological hallmark of neurodegenerative diseases, including β-amyloid in AD, α-synuclein in PD, and the transactive response DNA/RNA binding protein of 43kDa (TDP-43) in ALS. Furthermore, progression of the disease process accompanies the spreading of abnormal proteins. Extracellular proteins and RNAs, including mRNA, micro RNA, and circular RNA, which are present as a composite of exosomes or other forms, play a role in cell–cell communication, and the role of extracellular molecules in the cell-to-cell spreading of pathological processes in neurodegenerative diseases is now in the spotlight. Therefore, extracellular proteins and RNAs are considered potential biomarkers of neurodegenerative diseases, in particular ALS, in which RNA dysregulation has been shown to be involved in the pathogenesis. Here, we review extracellular proteins and RNAs that have been scrutinized as potential biomarkers of neurodegenerative diseases, and discuss the possibility of extracellular RNAs as diagnostic and therapeutic monitoring biomarkers of sporadic ALS.


2017 ◽  
Vol 8 (1) ◽  
pp. 22-32
Author(s):  
Nabanita Bhattacharyya ◽  
Subhajit Mondal ◽  
Mohammad Nasim Ali ◽  
Ramanuj Mukherjee ◽  
Anjan Adhikari ◽  
...  

It has been reported that Matrixmetalloproteinase-2 (MMP-2) is involved in the pathogenesis of cancer. The over expression of MMP-2 is associated with the progression of malignancy of several types of carcinoma. Human saliva is a biological fluid with several advantages for non-invasive diagnosis and prognosis of diseases. The aim of this study was to detect MMPs expression and activity in biological fluids (saliva, urine etc.) derived from breast cancer patients. Here, our results showed that the activity of MMP-2 was higher at the time before the surgery than after the saliva collected from the same patients. Therefore, we suggested that the highly active form of MMP-2 presented in saliva could be used as a novel potential biomarker for non-invasive diagnosis of breast cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Meng Li ◽  
Hongping Chen ◽  
Pengqi Yin ◽  
Jihe Song ◽  
Fangchao Jiang ◽  
...  

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.


2020 ◽  
Vol 48 (5) ◽  
pp. 2295-2305
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Peng Gao ◽  
Rongxue Peng ◽  
...  

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.


2020 ◽  
Vol 28 (3) ◽  
pp. 399-405
Author(s):  
Fabrizio Fontana ◽  
Olga A. Babenko

Aim of this letter is to attract the attention of journal readers to the study of exosomes as an important direction in the development of Oncology, in particular, in the diagnosis and treatment of prostate cancer. Exosomes are produced by tumor cells and regulate proliferation, metastasis, and the development of chemoresistance. Their extraction from biological fluids allows further use of these vesicles as potential biomarkers of prostate cancer. In the future, exosomes can be successfully used in the delivery of drugs and other anti-tumor substances to cancer cells.


2021 ◽  
Author(s):  
Xiaolong Chen ◽  
Yuanyi Deng ◽  
Gaihua Cao ◽  
Yifan Xiong ◽  
Danqun Huo ◽  
...  

MicroRNA-21 (miR-21) has been considered as a potential biomarker for cancer diagnosis and prognosis due to its highly expressed in tumors. Here, an analytical method which integrates the multiple cascaded...


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9006-9006
Author(s):  
Joshua Bauml ◽  
Byoung Chul Cho ◽  
Keunchil Park ◽  
Ki Hyeong Lee ◽  
EUN KYUNG CHO ◽  
...  

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.


2019 ◽  
Vol 20 (4) ◽  
pp. 1223-1228 ◽  
Author(s):  
Sumadi Lukman Anwar ◽  
Dwi Nur Indah Sari ◽  
Aprilia Indra Kartika ◽  
Meutia Srikandi Fitria ◽  
Dewi Sahfitri Tanjung ◽  
...  

Author(s):  
A. A. Mikheev ◽  
E. V. Shmendel ◽  
E. S. Zhestovskaya ◽  
G. V. Nazarov ◽  
M. A. Maslov

Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.


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