Zhang Weiran, Lin Xuefeng, Li Xin, Wang Meng, Sun Wei, Han Xingpeng, Sun Daqiang
Graduate School, Tianjin Medical University, Tianjin, China.
Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China.
J Gene Med. 2020 Sep;22(9):e3206. doi: 10.1002/jgm.3206. Epub 2020 Jun 11.
The 5-year survival rate of non-small cell lung cancer (NSCLC) is only 15%. Screening some combined gene mutations could predict the survival of NSCLC patients and also provide new ideas for the diagnosis and treatment of NSCLC. The present study aimed to identify signature mutations for survival prediction of NSCLC.
Clinical and gene mutation information for 949 NSCLC patients was downloaded from TCGA. High frequency mutation and common mutation genes were analyzed based on 1000 cancer related genes. The LASSO-COX model was used to screen gene mutation points and analyze their survival, and then a survival prediction model was established. Fifty NSCLC patients were collected and 1000 targeted genes were enriched by targeted next generation sequencing. The results were used to verify the combination of common mutation genes and the function of the survival model, and then to clarify their clinical significance.
Ten variables were screened out after LASSO-COX analysis, including age, tumor stage, EGFR c.[2,573 T>G], PIK3CA c.[1624G>A], TP53 c.[375G>T], TP53 c.[527G>T], TP53 c.[733G>T], TP53 c.[734G>T], TP53 c.[743G>T], NFE2L2 c.[100C>G]. Except for TP53 c.[743G>T] and NFE2L2 c.[100C>G], the residual six hot spot mutations of EGFR, PIK3CA and TP53 could be regarded as a signature mutations for forecasting the survival time of NSCLC.
The combination of six hot spot mutations of EGFR, PIK3CA and TP53 is expected to be used for predicting the survival time of NSCLC.
非小细胞肺癌（NSCLC）的5年生存率仅为15%。筛查一些联合基因突变可预测NSCLC患者的生存情况，也可为NSCLC的诊断和治疗提供新思路。本研究旨在鉴定用于NSCLC生存预测的特征性突变。
从TCGA下载949例NSCLC患者的临床和基因突变信息。基于1000个癌症相关基因分析高频突变和常见突变基因。使用LASSO-COX模型筛选基因突变点并分析其生存情况，进而建立生存预测模型。收集50例NSCLC患者，通过靶向二代测序富集1000个靶向基因。结果用于验证常见突变基因的组合及生存模型的功能，进而阐明其临床意义。
LASSO-COX分析后筛选出10个变量，包括年龄、肿瘤分期、EGFR c.[2,573 T>G]、PIK3CA c.[1624G>A]、TP53 c.[375G>T]、TP53 c.[527G>T]、TP53 c.[733G>T]、TP53 c.[734G>T]、TP53 c.[743G>T]、NFE2L2 c.[100C>G]。除TP53 c.[743G>T]和NFE2L2 c.[100C>G]外，EGFR、PIK3CA和TP53的其余六个热点突变可被视为预测NSCLC生存时间的特征性突变。
EGFR、PIK3CA和TP53的六个热点突变组合有望用于预测NSCLC的生存时间。
