TP53截断突变作为局部晚期口腔鳞癌诱导化疗预测性生物标志物的探讨

目的:检测TP53在局部晚期口腔鳞癌患者中的突变情况,探讨TP53截断突变能否作为生物标志物筛选诱导化疗获益患者。方法:选择2008—2014年收治的101例局部晚期口腔鳞癌患者,收集患者临床病理信息、肿瘤及正常对照新鲜冷冻或石蜡包埋样本。采用Ion Torrent PGM平台进行高通量测序,通过生物信息学软件进行突变识别及注释,采用SPSS 23.0软件包进行统计学分析。结果:101例患者中,男74例,女27例,中位年龄59岁,中位随访时间为34.9个月。平均测序深度肿瘤样本为2366乘,正常对照样本为2225乘。在73例患者中,检测出102个TP53非同义突变（等位基因频率≥3%）。与42例手术组口腔鳞癌患者相比,诱导化疗组（59例）无远处转移生存率较好（P=0.090）,但总生存率无显著差异。亚组分析显示,带有TP53截断突变的患者可以从诱导化疗中得到无远处转移生存获益（P=0.038）。结论:本研究未发现诱导化疗能整体提高局部晚期口腔鳞癌患者的生存期,但TP53截断突变可作为潜在的预测性生物标志物,筛选诱导化疗无远处转移生存获益的患者。

TP53 truncating mutation as a predictive biomarker for induction chemotherapy in patients with locally advanced oral squamous cell carcinoma

PURPOSE:To test the status of TP53 mutations in patients with locally advanced oral squamous cell carcinoma (OSCC) and investigate whether or not TP53 truncating mutation could be used as a predictive biomarker to screen patients who would benefit from induction chemotherapy. METHODS: One hundred and one patients with locally advanced OSCC treated in our hospital from 2008 to 2014 were included in this study. Their clinicopathologic information, frozen or formalin-fixed, paraffin-embedded samples of tumor and matched normal samples were collected. Using Ion PGM system, all samples were sequenced with high-throughput technology. Bioinformatics software was used to analyze and interpret the variants. SPSS 23.0 software package was used for statistical analysis. RESULTS: Among 101 patients, there were 74 men and 27 women with a median age of 59 years. The median follow-up time was 34.9 months. There were 102 TP53 non-synonymous mutations (allele frequency ≥3%) in 73 OSCC patients, with an average sequencing depth of 2366-fold in the tumor samples and 2225-fold in the matched normal samples. Compared with 42 patients who did not receive induction chemotherapy, 59 patients who received induction chemotherapy had a seemingly better distant metastasis free survival (P=0.090) while no significant difference in overall survival. Subgroup analysis showed that patients with TP53 truncating mutations could benefit from induction chemotherapy in distant metastasis free survival (P=0.038). CONCLUSIONS: Our study does not find that the patients with locally advanced OSCC could benefit from induction chemotherapy in overall survival, but TP53 truncating mutation could be used as a candidate of predictive biomarker to screen patients who would benefit from induction chemotherapy in distant metastasis free survival.