title: Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma.
abstract: BACKGROUND
  Codon 72 (Arg/Pro), the most frequently studied single nucleotide polymorphism (SNP) of p53 to date, is associated with the ability of the gene to induce cell apoptosis. The PI3K/Akt pathway plays an essential role in the transcriptional activation function of p53, and is an important factor in radiotherapy resistance. The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment.
  
  
  METHODS
  In total, 75 consecutive patients with locoregional NPC were enrolled. The p53 codon 72 SNP was identified from retrospectively collected paraffin-embedded biopsy specimens using Sanger sequencing. Expression patterns of p53, p21, 14-3-3σ, and pAkt proteins were investigated using immunohistochemical analyses. The effects of genetic polymorphisms and protein expression on progression-free survival (PFS) were evaluated using the Cox proportional hazards model, Kaplan-Meier method, and log-rank test.
  
  
  RESULTS
  The p53 codon 72 Pro/Pro carriers showed lower risk of disease progression (local recurrence and distant metastases) (HR: 0.300; 95% CI: 0.092-0.983; p=0.047). However, this association between the p53 codon 72 polymorphism and PFS was not significant in the pAkt-positive subgroup. No association was observed between protein expression of p53, p21 or 14-3-3σ and p53 codon72 polymorphisms. Notably, positive expression of p53 protein appeared to be correlated with poorer PFS among patients diagnosed as local regional lymph node metastasis (N+) before treatment (p=0.032).
  
  
  CONCLUSIONS
  The p53 codon 72 Pro/Pro genotype may be an effective independent prognostic marker for better outcome in patients with locoregional NPC. Based on the current findings, we hypothesize that pAkt weakens the predictive value of p53 codon 72 SNP in NPC. A combination of positive p53 protein expression and local regional lymph node metastasis may additionally be predictive of high risk of disease progression.
authors.affiliation: Department of Radiation and Oncology, Hunan Provincial Tumor Hospital & Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha 410013, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Xie
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Hekun
authors.initials: H
authors.lastname: Jin
authors.forename: Shuyu
authors.initials: S
authors.lastname: Ouyang
authors.forename: Jumei
authors.initials: J
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Xuping
authors.initials: X
authors.lastname: Xi
authors.forename: Junming
authors.initials: J
authors.lastname: Luo
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bingqiang
authors.initials: B
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma; D003062:Codon; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D011836:Radiation Tolerance / Q000235:genetics*; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt