LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia
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AuthorCuadros Celorrio, Marta Eugenia; García García, Daniel Jesús; Andrades Delgado, Álvaro; Arenas Molina, Alberto Manuel; Fernández Coira, Isabel; Baliñas Gavira, Carlos; Peinado, Paola; Rodríguez Lara, María Isabel; Álvarez Pérez, Juan Carlos; Ruiz-Cabello Osuna, Francisco; Medina Vico, Pedro Pablo
CTGFCCN2AL133346.1lncRNA expressionBiomarkerPediatric B-ALL
Cuadros, M., García, D. J., Andrades, A., Arenas, A. M., Coira, I. F., Baliñas-Gavira, C., ... & Medina, P. P. (2020). LncRNA-mRNA Co-Expression Analysis Identifies AL133346. 1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia. Cancers, 12(12), 3803. [doi:10.3390/cancers12123803]
SponsorshipAula de Investigación sobre la Leucemia infantil: Héroes contra la Leucemia the Ministry of Economy of Spain SAF2015-67919-R; Junta de Andalucía PIGE-0440-2019 Pl-0245-2017 PI-0135-2020; University of Granada PPJIA2019-06 B-CTS-126-UGR18; Spanish Association for Cancer Research (LAB-AECC); Spanish Ministry of Education, Culture and Sports FPU fellowship FPU17/00067 FPU17/01258; PhD "La Caixa Foundation" fellowship LCF/BQ/DE15/10360019; Marie Sklodowska Curie Actions postdoctoral fellowship (H2020-MSCA-IF-2018); "Fundacion Benefica Anticancer Santa Candida y San Francisco Javier" predoctoral fellowship
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. Abstract: 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 di erentially 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 di erential expression pattern and their strong correlation were validated in external B-ALL datasets (Therapeutically Applicable Research to Generate E ective 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.