Frontiers in Oncology (Jun 2022)

Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia

  • Didier Ismael May-Hau,
  • Didier Ismael May-Hau,
  • Diego Alberto Bárcenas-López,
  • Diego Alberto Bárcenas-López,
  • Juan Carlos Núñez-Enríquez,
  • Vilma Carolina Bekker-Méndez,
  • Fredy Omar Beltrán-Anaya,
  • Elva Jiménez-Hernández,
  • Mónica Patricia Ortíz-Maganda,
  • Francisco Xavier Guerra-Castillo,
  • Aurora Medina-Sanson,
  • Janet Flores-Lujano,
  • Jorge Alfonso Martín-Trejo,
  • José Gabriel Peñaloza-González,
  • Martha Margarita Velázquez-Aviña,
  • José Refugio Torres-Nava,
  • Gabriela Alicia Hernández-Echáurregui,
  • Rosa Martha Espinosa-Elizondo,
  • María de Lourdes Gutiérrez-Rivera,
  • Rodrigo Sanchez-Hernandez,
  • María Luisa Pérez-Saldívar,
  • Luz Victoria Flores-Villegas,
  • Laura Elizabeth Merino-Pasaye,
  • David Aldebarán Duarte-Rodríguez,
  • Minerva Mata-Rocha,
  • Omar Alejandro Sepúlveda-Robles,
  • Haydeé Rosas-Vargas,
  • Alfredo Hidalgo-Miranda,
  • Juan Manuel Mejía-Aranguré,
  • Juan Manuel Mejía-Aranguré,
  • Silvia Jiménez-Morales

DOI
https://doi.org/10.3389/fonc.2022.887766
Journal volume & issue
Vol. 12

Abstract

Read online

BackgroundB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whether LINC00173 is a biomarker in ALL and to explore its expression level in other human cancer types.MethodsA 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).ResultsA 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.ConclusionOur 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.

Keywords