LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia
Por:
Cuadros M, García DJ, Andrades A, Arenas AM, Coira IF, Baliñas-Gavira C, Peinado P, Rodríguez MI, Álvarez-Pérez JC, Ruiz-Cabello F, Camós-Guijosa M, Jiménez-Velasco A and Medina PP
Publicada:
1 dic 2020
Ahead of Print:
17 dic 2020
Resumen:
Simple Summary
Dysregulation of noncoding RNAs has been described in numerous types of cancers and it has been associated with oncogenic or tumor suppressor activities. However, the signature of clinically relevant noncoding RNAs in pediatric B-cell acute lymphoblastic leukemia is still poorly understood. In a search for long non-coding RNAs that characterize pediatric B-cell acute lymphoblastic leukemia, we found that the long non-coding RNA AL133346.1 and a neighbouring protein-coding mRNA (CCN2) were significantly over-expressed in leukemia samples compared to healthy bone marrow. Survival analysis showed that patients with high CCN2 expression had a significantly better prognosis. These data suggest that AL133346.1/CCN2 could be useful for discriminating subtypes of leukemia and that CCN2 expression could predict the prognosis of pediatric patients with B-cell acute lymphoblastic leukemia.
Pediatric acute B-cell lymphoblastic leukemia (B-ALL) constitutes a heterogeneous and aggressive neoplasia in which new targeted therapies are required. Long non-coding RNAs have recently emerged as promising disease-specific biomarkers for the clinic. Here, we identified pediatric B-ALL-specific lncRNAs and associated mRNAs by comparing the transcriptomic signatures of tumoral and non-tumoral samples. We identified 48 lncRNAs that were differentially expressed between pediatric B-ALL and healthy bone marrow samples. The most relevant lncRNA/mRNA pair was AL133346.1/CCN2 (previously known as RP11-69I8.3/CTGF), whose expression was positively correlated and increased in B-ALL samples. Their differential expression pattern and their strong correlation were validated in external B-ALL datasets (Therapeutically Applicable Research to Generate Effective Treatments, Cancer Cell Line Encyclopedia). Survival curve analysis demonstrated that patients with "high" expression levels of CCN2 had higher overall survival than those with "low" levels (p = 0.042), and this gene might be an independent prognostic biomarker in pediatric B-ALL. These findings provide one of the first detailed descriptions of lncRNA expression profiles in pediatric B-ALL and indicate that these potential biomarkers could help in the classification of leukemia subtypes and that CCN2 expression could predict the survival outcome of pediatric B-cell acute lymphoblastic leukemia patients.
Filiaciones:
Cuadros M:
Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Av. de la Investigación 11, 18016 Granada, Spain
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
García DJ:
Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Av. de la Investigación 11, 18016 Granada, Spain
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Andrades A:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
Arenas AM:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
Coira IF:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
Baliñas-Gavira C:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
Peinado P:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
Rodríguez MI:
Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Av. de la Investigación 11, 18016 Granada, Spain
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
Álvarez-Pérez JC:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
Ruiz-Cabello F:
Department of Biochemistry and Molecular Biology III and Immunology, University of Granada, Av. de la Investigación 11, 18016 Granada, Spain
Department of Clinical Analysis and Immunology, UGC Laboratorio Clínico, University Hospital Virgen de las Nieves, 18014 Granada, Spain
Camós-Guijosa M:
Hematology Laboratory, Institut de Recerca Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain
Leukemia and Other Pediatric Hemopathies, Developmental Tumors Biology Group, Institut de Recerca Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Jiménez-Velasco A:
Hematology Laboratory, Universitary Regional Hospital, Av. de Carlos Haya, 29010 Málaga, Spain
Medina PP:
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, Av. de la Ilustración 114, 18016 Granada, Spain
Instituto de Investigación Biosanitaria (ibs. Granada), Av. Fuerzas Armadas 2, 18014 Granada, Spain
Department of Biochemistry and Molecular Biology I, University of Granada, Av. de Fuente Nueva S/N, 18071 Granada, Spain
gold, Green Published
|