M Á Velázquez-Flores1, J M Rodríguez-Corona2, J E López-Aguilar3, G Siordia-Reyes4, G Ramírez-Reyes5, G Sánchez-Rodríguez5, R Ruiz Esparza-Garrido6. 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. 2. Technological Institute of Ciudad Victoria, National Technological Institute of Mexico, 87010, Ciudad Victoria, Tamaulipas, Mexico. 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. 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. 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. 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. rruizes@conacyt.mx.
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.
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.