A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool

Manterola, Lorea; Guruceaga, Elizabeth; Pérez-Larraya, Jaime Gállego; González-Huárriz, Marisol; Jáuregui, Patricia; Tejada, Sonia; Díez-Valle, Ricardo; Segura, Víctor; Samprón, Nicolás; Barrena, Cristina; Ruiz, Irune; Agirre, Amaia; Ayuso, Ángel; Rodríguez, Javier; González, Álvaro; Xipell, Enric; Matheu, Ander; Munáin, Adolfo López de; Tuñón, T; Zazpe, Idoya; Garcı́a-Foncillas, Jesús; Paris, Sophie; Delattre, Jean Yves; Alonso, Marta M.

doi:10.1093/neuonc/not218

Cited by 304 publications

(194 citation statements)

References 48 publications

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“…Consistent with this and with our findings, it has been shown that serum RNU6-1 levels are differentially expressed in serum from individuals with breast cancer compared to healthy controls [31]. In addition, a recent miRNA profiling study performed on the serum exosomes in individuals with glioblastoma identified RNU6-1 as a potential diagnostic cancer biomarker [32]. Thus, at least in the context of serum miRNA profiling studies in cancers, we propose that RNU6-1 is not suitable for use as a normalization control gene, and alternative methods of analysis are required.…”

Section: Discussionsupporting

confidence: 91%

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Chiam

Wang

Watson

et al. 2015

Journal of Gastrointestinal Surgery

122

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Section: Discussionsupporting

confidence: 91%

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Chiam

Wang

Watson

et al. 2015

Journal of Gastrointestinal Surgery

122

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“…GBM is one of the most deadly human malignancies worldwide and has increasing incidence with short survival rate and high mortality (15). Thus, the novel molecular mechanisms involved in the aggressive growth of GBM, and further new targeted therapies are required for prolonging the survival of glioma patients.…”

Section: Discussionmentioning

confidence: 99%

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

Huang¹,

Zhao²,

Weng³

et al. 2016

International Journal of Oncology

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Abstract. To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, Gene Ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients.

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“…13,[16][17][18] The initial studies in mice suggested that murine brain tumor exosomes had unique features that differentiated them from other exosomes, including expression of the mutated tumor antigen EGFRvIII and of immunosuppressive cytokine TGF-b. Further, these exosomes had immunomodulating properties and influenced tumor growth.…”

Section: E1008347-4mentioning

confidence: 99%

Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival

et al. 2015

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Exosomes in plasma of glioma patients hold promise as biomarkers of prognosis. We aimed to determine whether changes in total exosomal protein and mRNA expression levels could serve as surrogate markers of immunological and clinical responses in glioma patients receiving antitumor vaccines. Exosomes were isolated from pre/post-vaccine plasma specimens in 20/22 patients enrolled in a phase I/II trial with the antitumor vaccine. Exosomal protein content was analyzed and mRNA expression levels for 24 genes were simultaneously assessed by qRT-PCR. Pre-to postvaccination changes in exosomal protein and DCt values were correlated with immunological and clinical responses and survival using Spearman rank statistics and hazard ratios (HR). Exosomal protein levels positively correlated (p < 0.0043) with the WHO tumor grade at diagnosis. Protein levels were lower in post-vs. pre-vaccination exosome fractions. Post-therapy increases in tumor size were associated with elevations in exosome proteins in glioblastoma but not always in anaplastic astrocytoma (AA). Only exosomal DCt values for IL-8, TIMP-1, TGF-b and ZAP70 were significant (p < 0.04 to p < 0.001). The DCt for IL-8 and TGF-b mRNA positively correlated with post-vaccine immunologic responses to glioma antigens, while DCt for TIMP-1 mRNA was negatively correlated to DCt for IL-8 and TGF-b. Only DCt for IL-8 weakly correlated with OS and time to progression (TTP). In post-vaccine exosomes of the longest surviving patient with AA, mRNA for PD-1 was persistently elevated. Protein and mRNA expression levels for immune-related genes in plasma exosomes were useful in evaluating glioma patients' response to vaccination therapy.

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A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool

Abstract: Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.

Cited by 304 publications

References 48 publications

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients

Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival

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