LncRNA-mRNA Co-Expression Analysis Identifies AL133346.1/CCN2 as Biomarkers in Pediatric B-Cell Acute Lymphoblastic Leukemia

Abstract

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 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.