Prognostic model based on DAXX expression in gastric cancer patients with TP53 mutation and its predictive value for clinical outcomes
Objective To construct a prognosis model for gastric cancer(GC)patients with TP53 mutation based on death domain-associated protein(DAXX)expression,and to evaluate its predictive values.Methods The DNA variation characteristics of GC patients with wild-type and mutant TP53 were obtained from The Cancer Genome of Atlas(TCGA)database.The specimens of GC patients operated in the First Affiliated Hospital of Wenzhou Medical University from January 2014 to December 2016 were collected.The expression of p53 protein and DAXX protein were detected by immunohistochemistry.The survival of TP53 mutant GC patients with different DAXX expression status was analyzed.The influencing factors for survival of GC patients with mutant TP53 were analyzed by univariate and multivariate Cox analysis.Based on the prognostic factors a visual clinical prediction model was established and evaluated.Results The information from TCGA database showed that TP53 mutation was mainly concentrated in p53 DNA binding region and was closely related to the mutation level of titin,low-density lipoprotein receptor-related protein 1B and filaggrin in GC patients.The mRNA expression of DAXX was significantly increased in patients with TP53 mutation(P＜0.05).Immunohistochemical analysis showed that the cytoplasmic expression of DAXX in GC patients with TP53 mutation was significantly decreased(P＜0.01),while the nuclear expression and the nuclear-cytoplasmic ratio were significantly increased(all P＜0.01).The results of survival analysis showed that the prognosis of GC patients with TP53 mutation was relatively poor;however,the high expression of DAXX,especially in the nucleus,suggests a good prognosis in GC patients with TP53 mutation.The univariate and multivariate Cox analysis showed that in patients with TP53 mutation,age＞67,tumor stage was Ⅲ,and the low expression of DAXX in the nucleus were risk factors for the prognosis(all P＜0.10).The prediction model based on these three indicators may predict the prognosis of GC patients,the C index of the model was 0.740,indicating a good prediction value.Conclusion Based on DAXX nuclear expression and age,stage,and other clinicopathological features,the clinical prognosis of GC patients with TP53 mutation can be predicted.
万方数据
维普
