The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas

Guénaëlle Levallet (1, 2) , Fatéméh Dubois (1, 2) , Arthur Leclerc (3) , Edwige Petit (2) , Lien Bekaert (3) , Maxime Faisant (1) , Christian Creveuil (4) , Evelyne Emery (3) , Gérard Zalcman (5, 6, 7) , Emmanuèle Lechapt-Zalcman (8, 2, 9, 10)

1 Département de Pathologie [CHU Caen]
2 ISTCT - Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux
3 Service de Neurochirurgie [CHU Caen]
4 CHU Caen
5 U830 - Unité de génétique et biologie des cancers
6 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
7 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
8 Laboratoire d'Anatomie Pathologique [CHU Caen]
9 Inserm U955 - Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18)
10 Département de pathologie [Mondor]

IDH (isocitrate dehydrogenase) mutation, hypoxia, and neo-angiogenesis, three hallmarks of diffuse gliomas, modulate the expression of small non-coding RNAs (miRNA). In this paper, we tested whether pro-angiogenic and/or pro-hypoxic miRNAs could be used to monitor patients with glioma. The miRNAs were extracted from tumoral surgical specimens embedded in the paraffin of 97 patients with diffuse gliomas and, for 7 patients, from a blood sample too. The expression of 10 pro-angiogenic and/or pro-hypoxic miRNAs was assayed by qRT-PCR and normalized to the miRNA expression of non-tumoral brain tissues. We confirmed in vitro that IDH in hypoxia (1% O2, 24 h) alters pro-angiogenic and/or pro-hypoxic miRNA expression in HBT-14 (U-87 MG) cells. Then, we reported that the expression of these miRNAs is (i) strongly affected in patients with glioma compared to that in a non-tumoral brain; (ii) correlated with the histology/grade of glioma according to the 2016 WHO classification; and (iii) predicts the overall and/or progression-free survival of patients with glioma in univariate but not in a multivariate analysis after adjusting for sex, age at diagnosis, and WHO classification. Finally, the expression of miRNAs was found to be the same between the plasma and glial tumor of the same patient. This study highlights a panel of seven pro-angiogenic and/or pro-hypoxic miRNAs as a potential tool for monitoring patients with glioma.

Keywords: miRNA; hypoxia; angiogenesis; glioma

Domains: Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Genomics [q-bio.GN]

Guénaëlle Levallet, Fatéméh Dubois, Arthur Leclerc, Edwige Petit, Lien Bekaert, et al.. The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas. International Journal of Molecular Sciences, 2022, 23 (11), pp.6042. ⟨10.3390/ijms23116042⟩. ⟨hal-03699123⟩