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Expression of ABCB1, ABCC1 and 3 and ABCG2 in glioblastoma and their relevance in relation to clinical survival surrogates

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Abstract

Purpose

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumors in adults. Patients invariably relapse during or after first-line therapy and the median overall survival is 14.6 months. Such poor clinical response is partly ascribed to the activity of ATP-binding cassette (ABC) transporters. The activity of these proteins, severely reduces the amount of therapeutics that penetrates the tumor cells. We hypothesized that ABC transporter expression could correlate with survival surrogates. In this study, we assessed the expression of four commonly expressed ABC transporters in GBM samples and investigated if mRNA levels could serve as a prognostic biomarker.

Methods

Human specimens were analyzed by qPCR to assess ABCB1, ABCC1/3 and ABCG2 expression. Kaplan-Meier and multivariate analyses were then used to evaluate the correlation with overall survival (OS) and progression-free survival (PFS).

Results

Our cohort included 22 non-tumoral samples as well as 159 GBM tumor specimens. ABC transporters were significantly more expressed in GBM samples compared to non-tumoral tissue. Moreover ABCC1 and 3 mRNA expression were significantly increased at recurrence. Statistical analyses revealed that increased expression of either ABCC1 or ABCC3 did not confer a poorer prognosis. However, increased ABCC1 mRNA levels did correlate with a significantly shorter PFS.

Conclusion

In this manuscript, the analyses we conducted suggest that the expression of the four ABC transporters evaluated would not be suitable prognostic biomarkers. We believe that, when estimating prognosis, the plethora of mechanisms implicated in chemoresistance should be analyzed as a multi-facetted entity rather than isolated units.

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Data Availability

The datasets produced and analyzed during the current study are available upon reasonable request from the corresponding author.

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Acknowledgements

We thank Pr. Roscoe Klinck, Philippe Thibault, Mathieu Durand, Marie-Pierre Garant, Catherine Allard and Samuel Lemaire-Paquette for their consulting during qPCR and statistical data analyses. We also thank The Douglas Bell Canada Brain Bank for kindly providing the non-tumoral brain samples.

Funding

This work was supported by the National Bank research chair for the treatment of brain tumors as well as by the Fondation Coeur en Tête, the Fondation du CHUS and the Fondation de l’Université de Sherbrooke. Written informed consent was obtained from the individual participant included in this study. The authors have no relevant financial or non-financial conflict interests to disclose.

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Neurosurgery and Neuro-Oncology, Faculty of Medicine and Health Science, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada

    Laurent-Olivier Roy, Salman Aldakhil & David Fortin

  2. Department of Pharmacology, Faculty of Medicine and Health Science, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada

    Myriam Lemelin

  3. Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Science, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada

    Marie Blanchette

  4. Health Technology Assessment Unit, Centre Intégré Universitaire de Santé et de Services Sociaux de l’Estrie - Centre Hospitalier Universitaire de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada

    Marie-Belle Poirier

  5. Department of Surgery, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, Canada

    Marie-Belle Poirier

Authors
  1. Laurent-Olivier Roy
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  2. Myriam Lemelin
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  4. Marie-Belle Poirier
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  5. Salman Aldakhil
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  6. David Fortin
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Contributions

Conception/design: MBP, MB and DF. Development of methodology: MBP, MB, LOR and DF. Acquisition of data: ML, MB, LOR. Analysis and interpretation of data: LOR, ML, MBP, SA and DF. Writing, editing, and approval of the manuscript: LOR, SA and DF.

Corresponding author

Correspondence to David Fortin.

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The authors have no relevant financial or non-financial conflict interests to disclose.

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Written informed consent was obtained from all individual participants included in the study.

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Roy, LO., Lemelin, M., Blanchette, M. et al. Expression of ABCB1, ABCC1 and 3 and ABCG2 in glioblastoma and their relevance in relation to clinical survival surrogates. J Neurooncol 160, 601–609 (2022). https://doi.org/10.1007/s11060-022-04179-1

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