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. 2020 Mar 13;11(3):302.
doi: 10.3390/genes11030302.

Transcriptome Analysis Identifies LINC00152 as a Biomarker of Early Relapse and Mortality in Acute Lymphoblastic Leukemia

Diego Alberto Bárcenas-López  1 , Juan Carlos Núñez-Enríquez  2 , Alfredo Hidalgo-Miranda  3 , Fredy Omar Beltrán-Anaya  4 , Didier Ismael May-Hau  5 , Elva Jiménez-Hernández  6 , Vilma Carolina Bekker-Méndez  7 , Janet Flores-Lujano  2 , Aurora Medina-Sansón  8 , Edna Liliana Tamez-Gómez  9 , Víctor Hugo López-García  10 , José Ramón Lara-Ramos  11 , Nora Nancy Núñez-Villegas  6 , José Gabriel Peñaloza-González  12 , Luz Victoria Flores-Villegas  13 , Raquel Amador-Sánchez  14 , Rosa Martha Espinosa-Elizondo  15 , Jorge Alfonso Martín-Trejo  16 , Martha Margarita Velázquez-Aviña  12 , Laura Elizabeth Merino-Pasaye  13 , María Luisa Pérez-Saldívar  2 , David Aldebarán Duarte-Rodríguez  2 , José Refugio Torres-Nava  17 , Beatriz Cortés-Herrera  15 , Karina Anastacia Solís-Labastida  16 , Ana Itamar González-Ávila  14 , Jessica Denisse Santillán-Juárez  18 , Alejandra Jimena García-Velázquez  18 , Haydee Rosas-Vargas  19 , Minerva Mata-Rocha  19 , Omar Alejandro Sepúlveda-Robles  19 , Juan Manuel Mejía-Aranguré  2   20 , Silvia Jiménez-Morales  3
Affiliations

Transcriptome Analysis Identifies LINC00152 as a Biomarker of Early Relapse and Mortality in Acute Lymphoblastic Leukemia

Diego Alberto Bárcenas-López et al. Genes (Basel). .

Abstract

Evidence showing the role of long non-coding RNAs (lncRNAs) in leukemogenesis have emerged in the last decade. It has been proposed that these genes can be used as diagnosis and/or prognosis biomarkers in childhood acute lymphoblastic leukemia (ALL). To know if lncRNAs are associated with early relapse and early mortality, a microarray-based gene expression analysis in children with B-lineage ALL (B-ALL) was conducted. Cox regression analyses were performed. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated. LINC00152 and LINC01013 were among the most differentially expressed genes in patients with early relapse and early mortality. For LINC00152 high expression, the risks of relapse and death were HR: 4.16 (95% CI: 1.46-11.86) and HR: 1.99 (95% CI: 0.66-6.02), respectively; for LINC01013 low expression, the risks of relapse and death were HR: 3.03 (95% CI: 1.14-8.05) and HR: 6.87 (95% CI: 1.50-31.48), respectively. These results were adjusted by NCI risk criteria and chemotherapy regimen. The lncRNA-mRNA co-expression analysis showed that LINC00152 potentially regulates genes involved in cell substrate adhesion and peptidyl-tyrosine autophosphorylation biological processes. The results of the present study point out that LINC00152 could be a potential biomarker of relapse in children with B-ALL.

Keywords: LINC001013; LINC00152; acute lymphoblastic leukemia; early relapse; long noncoding RNA; microarray expression analysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Differentially expressed genes in pediatric patients with acute lymphoblastic leukemia with early relapse vs. non-relapsed cases. Rows display the genes identified, while the columns represent samples (early relapse: pink color and no-relapse: blue). Genes significantly down-regulated are displayed in green and up-regulated genes in red.
Figure 2
Figure 2
LncRNA–mRNA co-expression. Showing a positive (blue) or negative (brown) correlation between differentially expressed lncRNA and mRNA.
Figure 3
Figure 3
Kaplan–Meier plots (unadjusted) of overall survival for patients with pre-B acute lymphoblastic leukemia. Normalized array expression was used to determine either high (above median) or low (below median) expression of both lncRNAs (p-value was calculated with two-sided log-rank test).
Figure 4
Figure 4
Survival analysis between a low/high expression of LINC00152 with relapse.
See this image and copyright information in PMC

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