RNU6-1 in circulating exosomes differentiates GBM from non-neoplastic brain lesions and PCNSL but not from brain metastases
Montserrat Puigdelloses (1, 2, 3) , Marisol González-Huárriz (1, 2, 4) , Marc García-Moure (1, 2, 4) , Naiara Martínez-Vélez (1, 2, 4) , Inés Esparragosa Vázquez (1, 2, 3) , Jordi Bruna (5) , Beatriz Zandio (6) , Amaia Agirre (7) , Miguel Marigil (8) , Gregorio Petrirena (9) , Jorge M Nuñez-Córdoba (10, 11) , Sonia Tejada-Solís (1, 12) , Ricardo Díez-Valle (1, 12) , Jaime Gállego-Culleré (6) , Eduardo Martínez-Vila (1, 2, 3) , Ana Patiño-García (1, 2, 4) , Marta M Alonso (1, 2, 4) , Jaime Gállego Pérez-Larraya (1, 2, 3)
(1) Health Research Institute of Navarra (IDISNA), Pamplona, Spain.
(2) Program in Solid Tumors, Center for the Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
(3) Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain.
(4) Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.
(5) Department of Neurology, Hospital de Bellvitge, Barcelona, Spain.
(6) Department of Neurology, Complejo Hospitalario de Navarra, Pamplona, Spain.
(7) POLYMAT, University of the Basque Country, San Sebastian, Spain.
(8) Division of Neurosurgery, Lariboisière University Hospital, Paris, France.
(9) Service de Neuro-Oncologie, Hôpital de la Timone, Marseille, France.
(10) Research Support Service, Central Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain.
(11) Department of Preventive Medicine and Public Health, Medical School, Universidad de Navarra, Pamplona, Spain.
(12) Department of Neurosurgery, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
Background: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Circulating biomarkers may assist in the processes of differential diagnosis and response assessment. GBM cells release extracellular vesicles containing a subset of proteins and nucleic acids.
We previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to healthy subjects. In this exploratory study, we investigated the role of this small noncoding RNA as a diagnostic biomarker for GBM versus other brain lesions with some potential radiological similarities.
Methods: We analyzed the expression of RNU6-1 in circulating exosomes of GBM patients (n = 18), healthy controls (n = 30), and patients with subacute stroke (n = 30), acute/subacute hemorrhage (n = 30), acute demyelinating lesions (n = 18), brain metastases (n = 21), and primary central nervous system lymphoma (PCNSL; n = 12) using digital droplet PCR.
Results: Expression of RNU6-1 was significantly higher in GBM patients than in healthy controls (P = .002). RNU6-1 levels were also significantly higher in exosomes from GBM patients than from patients with non-neoplastic lesions (stroke [P = .05], hemorrhage [P = .01], demyelinating lesions [P = .019]) and PCNSL (P = .004). In contrast, no significant differences were found between patients with GBM and brain metastases (P = .573).
Receiver operator characteristic curve analyses supported the role of this biomarker in differentiating GBM from subacute stroke, acute/subacute hemorrhage, acute demyelinating lesions, and PCNSL (P < .05), but again not from brain metastases (P = .575).
Conclusions: Our data suggest that the expression of RNU6-1 in circulating exosomes could be useful for the differentiation of GBM from non-neoplastic brain lesions and PCNSL, but not from brain metastases.
CITA DEL ARTÍCULO Neurooncol Adv . 2020 Jan 31;2(1):vdaa010.
doi: 10.1093/noajnl/vdaa010. eCollection Jan-Dec 2020