基于生存分析模型抗细胞凋亡因子表达水平与胃癌放疗敏感相关性分析

Low expression of DAD1 associated with radiosensitivity of patients with gastric cancer based on survival model

目的抗细胞凋亡因子(defender against cell death 1,DAD1)具有抑制凋亡的功能,可能与肿瘤的发生以及预后有关,可作为肿瘤治疗和预后的重要靶标。本研究旨在探讨DAD1与胃癌放疗敏感性关系。方法采用肿瘤基因图谱(the cancer genome atlas,TCGA)公开的胃癌数据库,经数据清理后获得371例数据,采用交叉验证方法,将全部数据完全随机分为测试数据和验证数据2份。在不同DAD1表达水平下,采用Cox模型分析放疗和未接受放疗组患者生存率差异。结果分析结果表明,DAD1表达与胃癌患者总生存差异无统计学意义的关联;测试和验证数据结果表明,高表达DAD1的胃癌患者在放疗与非放疗组间总生存差异无统计学意义,多因素调整后差异也无统计学意义,测试数据和验证数据调整后HR=1.00,95%CI:0.30~3.34,P=1.00和HR=0.64,95%CI:0.26~1.60,P=0.34;而DAD1低表达的胃癌患者,接受放疗较未接受放疗的患者获得了显著的生存收益,测试数据和验证数据调整后HR=0.20,95%CI:0.04~0.68,P=0.009 7和HR=0.09,95%CI:0.01~0.52,P=0.007 4。结论低表达DAD1与胃癌放疗敏感性存在统计学意义的关联,低表达DAD1患者在接受放疗后生存率提高,提示DAD1可作为胃癌精准放疗的潜在有效分子标志物。

OBJECTIVE Defender against cell death 1(DAD1)has the function of inhibiting apoptosis.Studies have shown that apoptotic factors may be related to the occurrence and prognosis of tumors,and may be an important target for the treatment and prognosis of tumors.The purpose of this study was to investigate the association between the expression level of DAD1 and radiosensitivity.METHODS We used the gastric cancer data from TCGA.After data cleaning step,a total 371 patients were included in the present study.To validate our assumption,we randomly split the data to two parts,one as testing data,another one as validation data.The Cox regression model was used to evaluate the difference between radiotherapy and nonradiotherapy group,under different expression level of DAD1.RESULTS The results had shown that the expression level did not associate with overall survival,both on testing and validation data.For patients with high expression level of DAD1,there was no significant difference between radiotherapy and nonradiotherapy group.The adjusted HR=1.00,95%CI:0.30-3.34,P=1.00 and HR=0.64,95%CI:0.26-1.60,P=0.34,for testing and validation data,respectively.For patients with low expression of DAD1,significant difference was observed between radiotherapy and nonradiotherapy group.The adjusted HR=0.20,95%CI:0.04-0.68,P=0.009 7 and HR=0.09,95%CI:0.01-0.52,P=0.007 4,for testing and validation data,respectively.CONCLUSIONS These results suggested that low expression of DAD1 strongly associated with radiosensitivity.Patients with low expression of DAD1 would get better survival if they received radiotherapy.The results suggested that the expression of DAD1 might be a potential biomarker for radiotherapy treatment of gastric cancer.