Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement
M Á Velázquez-Flores1, J M Rodríguez-Corona2, J E López-Aguilar3
1Non-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.
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.
Insights
Non-coding RNAs (ncRNAs) are involved in diffuse intrinsic pontine gliomas (DIPGs). XIST and XIST-210 show potential as prognostic biomarkers for DIPGs, especially in girls with longer survival.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Diffuse intrinsic pontine gliomas (DIPGs) are highly fatal pediatric brainstem tumors.
- Understanding the molecular mechanisms of DIPG formation and progression is crucial for developing effective treatments.
Purpose of the Study:
- To identify novel molecular features, specifically non-coding RNAs (ncRNAs), involved in DIPG pathogenesis.
- To establish an ncRNA signature for DIPGs.
Main Methods:
- Transcriptome analysis of DIPGs using the HTA2.0 array.
- Comparison of DIPG expression profiles with pediatric non-brainstem astrocytoma data (GSE72269).
- Quantitative PCR (qPCR) assays to validate gene expression levels.
Main Results:
- Over 50% of differentially expressed transcripts in DIPGs were ncRNAs.
- A DIPG-specific ncRNA signature was proposed.
- LncRNAs XIST and XIST-210, and HBII-52/HBII-85 snoRNA clusters were downregulated in DIPGs.
- XIST downregulation was observed across non-brainstem astrocytomas and in DIPGs affecting boys; however, DIPGs in girls showed variable XIST expression.
- Higher XIST expression correlated with longer survival in girls with DIPGs.
Conclusions:
- ncRNAs play a significant role in DIPGs.
- ncRNA expression profiles can differentiate DIPGs from non-neoplastic tissues and non-brainstem astrocytomas.
- ncRNAs, particularly XIST and XIST-210, hold potential as diagnostic and prognostic biomarkers for DIPGs.
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