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

doi:10.19438/j.cjoms.2018.04.006

中国口腔颌面外科杂志 ›› 2018, Vol. 16 ›› Issue (4): 322-327.doi: 10.19438/j.cjoms.2018.04.006

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

付永¹, 马捷¹, 刘莹¹, 谈亦然¹, 琚梧桐¹, 孙文文¹, 赵铜超¹, 王旻¹, 王丽珍², 李江², 张陈平¹, 张志愿¹, 钟来平¹

1.上海交通大学医学院附属第九人民医院·口腔医学院口腔颌面-头颈肿瘤科,
2.口腔病理科, 国家口腔疾病临床研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所

收稿日期:2018-04-18 修回日期:2018-07-09 出版日期:2018-07-20 发布日期:2018-08-09
通讯作者: 钟来平,E-mail：zhonglaiping@163.com
作者简介:付永（1990-）,男,硕士研究生,E-mail：fy114@foxmail.com
基金资助:
国家自然科学基金（81472519,81672660）; 上海市教育委员会曙光计划（17SG18）

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

FU Yong¹, MA Jie¹, LIU Ying¹, TAN Yi-ran¹, JU Wu-tong¹, SUN Wen-wen¹, ZHAO Tong-chao¹, WANG Min¹, WANG Li-zhen², LI Jiang², ZHANG Chen-ping¹, ZHANG Zhi-yuan¹, ZHONG Lai-ping¹

1.Department of Oromaxillofacial Head and Neck Oncology,
2.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 Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology. Shanghai 200011, China;

Received:2018-04-18 Revised:2018-07-09 Online:2018-07-20 Published:2018-08-09

摘要/Abstract

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。

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

Abstract: 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.

Key words: Oral squamous cell carcinoma, TP53 truncating mutation, Distant metastasis free survival, Biomarker, Induction chemotherapy

中图分类号:

R739.8

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. 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[J]. 中国口腔颌面外科杂志, 2018, 16(4): 322-327.

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. TP53 truncating mutation as a predictive biomarker for induction chemotherapy in patients with locally advanced oral squamous cell carcinoma[J]. China J Oral Maxillofac Surg, 2018, 16(4): 322-327.

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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

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

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