To explore the effects of Wilms tumor 1-associating protein (WTAP) rs7766006 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors.

Pediatric patients with brain tumors who received chemotherapy at our hospital were included as study subjects. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used for WTAP rs7766006 genotyping. Clinical data collected included chemotherapy toxicities and tumor progression. The associations of WTAP rs7766006 G>T polymorphisms with chemotherapy toxicities and progression-free survival (PFS) were analyzed. The expression of WTAP in brain tumors and its prognostic significance, and the potential mechanism of rs7766006 G>T polymorphisms in WTAP expression were explored based on bioinformatics methods.

Among the 107 children with brain tumors included, the rs7766006 GG homozygous, GT heterozygous, and TT homozygous genotypes accounted for 40.19% (43 cases/107 cases), 44.86% (48 cases/107 cases) and 14.95% (16 cases/107 cases), respectively. The frequencies of G and T alleles were 62.62% (134 cases/214 cases) and 37.38% (80 cases/214 cases) respectively. The incidence rates of mucositis in the GG, GT, and TT genotype groups were 53.49% (23cases/43 cases), 27.08% (13 cases/48 cases) and 43.75% (7 caes/16 cases), respectively. The incidence rates of coagulation disorders in three groups were 18.61% (8 cases/43cases), 2.08% (1 case/48 cases) and 6.25% (1 case/16 cases), respectively. The difference in the incidence rates of the two chemotherapy toxicities mentioned above between the GG and GT genotypes was statistically significant (all P<0.05). However, there were no significant differences in the incidence of other chemotherapy toxicities among the three groups (all P>0.05). The disease progression rates for the GG, GT, and TT genotype groups were 65.12% (28 cases/43 cases), 43.75% (21 cases/48 cases), and 62.50% (10 cases/16 cases), respectively. The risk of disease progression in children with the GG genotype was significantly higher than in those with the GT genotype (P<0.05). Bioinformatics analysis showed that the WTAP expression in brain tumors 6.00±0.66 was significantly higher than that in normal tissues 4.63±1.34 (P<0.001). The median overall survivals for the WTAP high-expression group and the low-expression group were 537 and 2 835 days, respectively (P<0.001). The rs7766006 polymorphism was located in the exonic splicing enhancer site and possibly regulated WTAP expression by affecting alternative splicing.

WTAP rs7766006 GG genotype might be a risk factor for oral mucositis, coagulation disorders, and progression in children with brain tumors.