MMP-1, UCH-L1, and 20S Proteasome as Potential Biomarkers Supporting the Diagnosis of Brain Glioma

The diagnosis of brain gliomas is mainly based on imaging methods. The gold standard in this area is MRI. Recommendations for the prevention, diagnosis, and treatment of gliomas are periodically modified and updated. One of the diagnostic techniques used when a brain glioma is suspected is liquid biopsy. However, this technique requires further development to confirm its effectiveness. This paper presents a proposal of three potential biomarkers of brain gliomas—extracellular matrix metalloproteinase-1 (MMP-1), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and the 20S proteasome—which were quantified in blood plasma using SPRi biosensors. A statistical analysis of the results indicated no significant changes in the concentrations between the control group (K) and grades G1 and G2, and similarly between grades G3 and G4. However, the differences in the concentrations between the groups K/G1/G2 and G3/G4 were statistically significant. A positive average correlation was found between the concentrations of the proteins and the patient’s age. The individual tested proteins were also highly correlated with each other. Our work proposes a new diagnostic technique that may aid in the diagnosis of brain gliomas.

[1]  R. Gothalwal,et al.  The road-map for establishment of a prognostic molecular marker panel in glioma using liquid biopsy: current status and future directions , 2022, Clinical and Translational Oncology.

[2]  J. Cryan,et al.  The blood-brain barrier in aging and neurodegeneration , 2022, Molecular Psychiatry.

[3]  S. Flora,et al.  Surface plasmon resonance: A promising approach for label-free early cancer diagnosis. , 2022, Clinica chimica acta; international journal of clinical chemistry.

[4]  S. Maksoud The role of the ubiquitin proteasome system in glioma: analysis emphasizing the main molecular players and therapeutic strategies identified in glioblastoma multiforme. , 2021, Molecular Neurobiology.

[5]  J. Mesirov,et al.  Pten Deficiency Leads To Proteasome Addiction, A Novel Vulnerability In Glioblastoma. , 2021, Neuro-oncology.

[6]  G. Reifenberger,et al.  EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood , 2020, Nature Reviews Clinical Oncology.

[7]  M. Weller,et al.  Liquid biopsies for diagnosing and monitoring primary tumors of the central nervous system. , 2020, Cancer letters.

[8]  F. Rashid,et al.  Proteasome inhibition—a new target for brain tumours , 2019, Cell Death Discovery.

[9]  C. Post,et al.  Ubiquitin C‐Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine‐Based Inhibitor , 2019, ChemBioChem.

[10]  Leland S. Hu,et al.  Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data , 2018, Neuro-oncology.

[11]  Yidong Chen,et al.  Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is associated with stem-like cancer cell functions in pediatric high-grade glioma , 2017, PloS one.

[12]  H. Kornblum,et al.  Molecular markers in glioma , 2017, Journal of Neuro-Oncology.

[13]  Benjamin M. Ellingson,et al.  Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials , 2017, Neurotherapeutics.

[14]  Ian Law,et al.  Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. , 2016, Neuro-oncology.

[15]  E. Gorodkiewicz,et al.  The development of a matrix metalloproteinase-1 biosensor based on the surface plasmon resonance imaging technique , 2016 .

[16]  Johan Svensson,et al.  Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease , 2016, Dementia and Geriatric Cognitive Disorders Extra.

[17]  P. Laudanski,et al.  Development of surface plasmon resonance imaging biosensors for detection of ubiquitin carboxyl-terminal hydrolase L1. , 2015, Analytical biochemistry.

[18]  H. Colman,et al.  Glioma biology and molecular markers. , 2015, Cancer treatment and research.

[19]  Ivan Dikic,et al.  Ubiquitination in disease pathogenesis and treatment , 2014, Nature Medicine.

[20]  Paul H. Huang,et al.  The Pathobiology of Collagens in Glioma , 2013, Molecular Cancer Research.

[21]  P. Vlachostergios,et al.  The ubiquitin-proteasome system in glioma cell cycle control , 2012, Cell Division.

[22]  E. Gorodkiewicz,et al.  SPR imaging biosensor for the 20S proteasome: sensor development and application to measurement of proteasomes in human blood plasma , 2011, Mikrochimica acta.

[23]  H. Fillmore,et al.  Epidermal growth factor induces matrix metalloproteinase-1 (MMP-1) expression and invasion in glioma cell lines via the MAPK pathway , 2011, Journal of Neuro-Oncology.

[24]  S. Hofer,et al.  Molecular markers in gliomas: impact for the clinician , 2010, Targeted Oncology.

[25]  N. Pullen,et al.  Induction of matrix metalloproteinase-1 and glioma cell motility by nitric oxide , 2009, Journal of Neuro-Oncology.

[26]  K. Wada,et al.  Aberrant Interaction between Parkinson Disease-associated Mutant UCH-L1 and the Lysosomal Receptor for Chaperone-mediated Autophagy* , 2008, Journal of Biological Chemistry.

[27]  W. Roggendorf,et al.  Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas , 2008, Neuroscience Research.

[28]  W. Broaddus,et al.  Association of a single nucleotide polymorphism in the matrix metalloproteinase‐1 promoter with glioblastoma , 2005, International journal of cancer.