脑肿瘤患儿WTAP rs7766006位点遗传多态性与化疗毒性及临床预后的相关性研究OA

Objective To explore the effects of Wilms tumor 1-associating protein(WTAP)rs7766006 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors.Methods 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.Results 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.Conclusion WTAP rs7766006 GG genotype might be a risk factor for oral mucositis,coagulation disorders,and progression in children with brain tumors.