摘要
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。
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 were102 TP53 non-synonymous mutations（allele frequency ≥3%） in 73 OSCC patients, with an average sequencing depth of2366-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.
作者
付永
马捷
刘莹
谈亦然
琚梧桐
孙文文
赵铜超
王旻
王丽珍
李江
张陈平
张志愿
钟来平
FU Yong;MA Jie;LIU Ying;TAN Yi-ran;JU Wu-tong;SUN Wen-wen;ZHAO Tong-chao;WANG Min;WANG Li-zhen;LI Jiang;ZHANG Chen-ping;ZHANG Zhi-yuan;ZHONG Lai-ping(Department of Oromaxillofacial Head and Neck Ontology;Department of Oral Pathology,Shanghai Ninth People＇s Hospital,College of Stomatology,Shanghai Jiao Tong University School of Medicine;National Clinical Research Center For Oral Disease;Shanghai Key Laboratory of Stomatology ＆ Shanghai Research Institute of Stomatology.Shanghai 200011,Chin)
出处
《中国口腔颌面外科杂志》
CAS
2018年第4期322-327,共6页
China Journal of Oral and Maxillofacial Surgery
基金
国家自然科学基金(81472519,81672660)
上海市教育委员会曙光计划(17SG18)
关键词
口腔鳞状细胞癌
TP53截断突变
无远处转移生存
生物标志物
诱导化疗
Oral squamous cell carcinoma
TP53 truncating mutation
Distant metastasis free survival
Biomarker
Induction chemotherapy
