Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia.
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May-Hau Didier Ismael, Bárcenas-López Diego Alberto, Núñez-Enríquez Juan Carlos, Bekker-Méndez Vilma Carolina, Beltrán-Anaya Fredy Omar, Jiménez-Hernández Elva, Ortíz-Maganda Mónica Patricia, Guerra-Castillo Francisco Xavier, Medina-Sanson Aurora, Flores-Lujano Janet, Martín-Trejo Jorge Alfonso, Peñaloza-González José Gabriel, Velázquez-Aviña Martha Margarita, Torres-Nava José Refugio, Hernández-Echáurregui Gabriela Alicia, Espinosa-Elizondo Rosa Martha, Gutiérrez-Rivera María de Lourdes, Sanchez-Hernandez Rodrigo, Pérez-Saldívar María Luisa, Flores-Villegas Luz Victoria, Merino-Pasaye Laura Elizabeth, Duarte-Rodríguez David Aldebarán, Mata-Rocha Minerva, Sepúlveda-Robles Omar Alejandro, Rosas-Vargas Haydeé, Hidalgo-Miranda Alfredo, Mejía-Aranguré Juan Manuel, Jiménez-Morales Silvia
Аннотация
METHODS: A nested case-control study including Mexican children with BCP-ALL was conducted. LINC00173 expression was evaluated by qRT-PCR using hydrolysis probes. To validate our findings, RNA-seq expression data from BCP-ALL and normal tissues were retrieved from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) repositories, respectively. LINC00173 expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA).
RESULTS: A lower expression of LINC00173 in BCP-ALL cases compared to normal subjects was observed (p < 0.05). ALL patients who carry the TCF3/PBX1 fusion gene displayed lower expression of LINC00173 in contrast to other BCP-ALL molecular subtypes (p < 0.04). LINC00173 underexpression was associated with a high risk to relapse (HR = 1.946, 95% CI = 1.213-3.120) and die (HR = 2.073, 95% CI = 1.211-3.547). Patients with TCF3/PBX1 and underexpression of LINC00173 had the worst prognosis (DFS: HR = 12.24, 95% CI = 5.04-29.71; OS: HR = 11.19, 95% CI = 26-32). TCGA data analysis revealed that underexpression of LINC00173 is also associated with poor clinical outcomes in six new reported tumor types.
CONCLUSION: Our findings suggest that LINC00173 is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of LINC00173 and TCF3/PBX1 and the risk to relapse and die in BCP-ALL, which is worse in TCF3/PBX1-positive cases displaying underexpression of LINC00173. Experimental studies are needed to provide insight into the LINC00173 and TCF3/PBX relationship.