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Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement

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Abstract

Purpose

Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments.

Methods

We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269).

Results

More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls’ with longer survival positively correlated with XIST expression.

Conclusions

The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers.

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Acknowledgements

We thank Miguel Araujo and Elizabeth Morales for their technical support. This research was supported by FIS/IMSS/PROT/G17/1673 from the Instituto Mexicano del Seguro Social (IMSS). Special thanks to SINTAGMA TRANSLATIONS for English language correction.

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Authors and Affiliations

  1. Non-coding RNAs Laboratory, Medical Research Unit in Human Genetics, Children’s Hospital “Dr. Silvestre Frenk Freund”, National Medical Center XXI Century, Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS), 06720, Mexico City, CDMX, Mexico

    M. Á. Velázquez-Flores

  2. Technological Institute of Ciudad Victoria, National Technological Institute of Mexico, 87010, Ciudad Victoria, Tamaulipas, Mexico

    J. M. Rodríguez-Corona

  3. Medical Chief of the Children’s Hospital “Dr. Silvestre Frenk Freund”, National Medical Center XXI Century, Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS), 06720, Mexico City, CDMX, Mexico

    J. E. López-Aguilar

  4. Pathology Department, Children’s Hospital “Dr. Silvestre Frenk Freund”, National Medical Center XXI Century, Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS), 06720, Mexico City, CDMX, Mexico

    G. Siordia-Reyes

  5. Neurosurgery Department, Children’s Hospital “Dr. Silvestre Frenk Freund”, National Medical Center XXI Century, Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS), 06720, Mexico City, CDMX, Mexico

    G. Ramírez-Reyes & G. Sánchez-Rodríguez

  6. Catedrática CONACyT, Non-coding RNAs Laboratory, Medical Research Unit in Human Genetics, Children’s Hospital “Dr. Silvestre Frenk Freund”, National Medical Center XXI Century, Mexican Institute of Social Security (Instituto Mexicano del Seguro Social, IMSS) 06720 Mexico City CDMX Mexico, Av. Cuauhtémoc 330, Doctores, 06720, Mexico City, CDMX, Mexico

    R. Ruiz Esparza-Garrido

Authors
  1. M. Á. Velázquez-Flores
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  2. J. M. Rodríguez-Corona
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  3. J. E. López-Aguilar
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  5. G. Ramírez-Reyes
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  6. G. Sánchez-Rodríguez
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  7. R. Ruiz Esparza-Garrido
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Contributions

RRE and MV designed the study, performed the experiments, and analyzed the data. Also, these authors wrote and reviewed the manuscript. JR performed the bioinformatic analysis and reviewed the final version of the manuscript. JL, GR, and GS provided the samples and the clinical data of the patients included in the study. They also reviewed the final version of the manuscript. GS performed the immunohistopathological and immunohistochemical analysis, and reviewed the final version of the manuscript.

Corresponding author

Correspondence to R. Ruiz Esparza-Garrido.

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Conflict of interest

All authors declare no conflict of interest.

Ethical standard

The project has the approval of the hospital de Pediatría, Centro Médico Nacional Siglo XXI, IMSS: Ethics in Security Research (R-2014-3603-247) which is in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Research involving human participants or animals

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Written consent forms were obtained from participants who provided fresh samples of tissue for the HTA 2.0 array and the qPCR component of the study.

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Velázquez-Flores, M.Á., Rodríguez-Corona, J.M., López-Aguilar, J.E. et al. Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement. Clin Transl Oncol 23, 501–513 (2021). https://doi.org/10.1007/s12094-020-02443-2

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  • DOI: https://doi.org/10.1007/s12094-020-02443-2

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