AUTHOR=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 

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

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.887766

DOI=10.3389/fonc.2022.887766

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>B-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 <italic>LINC00173</italic> is a biomarker in ALL and to explore its expression level in other human cancer types.</p></sec><sec><title>Methods</title><p>A nested case–control study including Mexican children with BCP-ALL was conducted. <italic>LINC00173</italic> 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. <italic>LINC00173</italic> expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA).</p></sec><sec><title>Results</title><p>A lower expression of <italic>LINC00173</italic> in BCP-ALL cases compared to normal subjects was observed (<italic>p</italic> &lt; 0.05). ALL patients who carry the <italic>TCF3/PBX1</italic> fusion gene displayed lower expression of <italic>LINC00173</italic> in contrast to other BCP-ALL molecular subtypes (<italic>p</italic> &lt; 0.04). <italic>LINC00173</italic> 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 <italic>TCF3/PBX1</italic> and underexpression of <italic>LINC00173</italic> 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 <italic>LINC00173</italic> is also associated with poor clinical outcomes in six new reported tumor types.</p></sec><sec><title>Conclusion</title><p>Our findings suggest that <italic>LINC00173</italic> is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of <italic>LINC00173</italic> and <italic>TCF3/PBX1</italic> and the risk to relapse and die in BCP-ALL, which is worse in <italic>TCF3/PBX1-</italic>positive cases displaying underexpression of <italic>LINC00173.</italic> Experimental studies are needed to provide insight into the <italic>LINC00173</italic> and <italic>TCF3/PBX</italic> relationship.</p></sec>