Análise da expressão dos genes WRAP53 e hTERT como potenciais biomarcadores moleculares em pacientes com Leucemia Mieloide Aguda

Abstract

Acute myeloid leukemia (AML) is one of the most common types of cancer that mainly affects adults, and is characterized by clonal disturbance in hematopoietic cells, marked by rapid progression and the presence of several distinct genetic profiles. Genomic instability is an important characteristic of AML and plays a significant role in the development and progression of the disease. Hyperactivity of the telomerase enzyme, a characteristic associated with genomic instability, appears as a factor that predisposes to hematologic malignancies, since the genes that make up the telomerase complex are frequently mutated in acute myeloid leukemia. Several studies have shown the role of the WRAP53 gene in genomic stability, given its biological role in activities such as DNA repair, regulation of TP53 and interaction with telomerase. In this context, the present study aimed to molecularly evaluate the expression of the WRAP53 and hTERT genes to present them as possible new biomarkers in AML. For this purpose, the study included a sample of 110 patients diagnosed with AML who were stratified and classified according to the guidelines of the World Health Organization (WHO). For statistical analysis based on the clinical and epidemiological data of the patients, the Chi-square test was applied. Gene expression data analysis, using the RT-qPCR technique, was performed by the delta-delta CT method. Normality was assessed by the Kolmogorov-Smirnov or Shapiro-Wilk test and was applied to each specific group. Outliers were removed based on the upper and lower fence of interquartile range. Differences in continuous variables were analyzed using the Mann-Whitney or Unpaired t-test test to compare medians between two groups and the Kruskal-Wallis test or one-way ANOVA to compare medians among variables with three or more groups. The correlation between two continuous variables was determined using the Pearson correlation coefficient. Survival probabilities were estimated by the Kaplan-Meier method For all tests, a significance level of 95% (p≤0.05) was assumed. After the analyses, it was identified that the study participants had a mean age over 50 years and that the incidence of AML did not differ between the gender. We identified decreased WRAP53 expression in AML patients compared to control patients (p < 0.0001), while for hTERT we did not identify differences in expression (p = 0,2524). The correlation analysis indicated a positive and moderate relationship between the analyzed variables (r = 0.4374). Regarding the clinical parameters analyzed, statistical differences were observed for WRAP53 in the parameter of gender (p = 0,0322) and age (p = 0,0496), while for hTERT in the parameters analyzed no differences were observed. The overall survival analysis did not reveal significance for either WRAP53 (p = 0.150) or hTERT (p = 0.316). The results presented demonstrate a downregulation of WRAP53 in the studied sample and that, furthermore, the expression of the WRAP53 and hTERT genes were correlated. In addition, the expression of hTERT, which is already indicated as a biomarker in AML, could not be correlated with the clinical characteristics analyzed that were analyzed in this study.