[Hypomethylation of DAPL1 associated with prognosis of lung cancer patients with EGFR Del19 mutation].

Objective: To investigate the effect of apoptosis-associated protein kinase-like 1 (DAPL1) hypomethylation on prognosis of lung cancer patients with epidermal growth factor receptor gene exon 19 deletion (EGFR Del19) mutation. Methods: The clinicopathological data of lung cancer patients in databases of genomic data sharing (GDC) TCGA lung adenocarcinoma, TCGA lung adenocarcinoma, and TCGA lung cancer were collected to analyze the effect of DAPL1 methylation level on the prognosis of patients with EGFR Del19 mutation. Linear regression model was used for correlation analysis, Kaplan-Meier method was used to draw the survival curve, and the difference of survival curve between the two groups was tested by Log rank. Results: In GDC TCGA lung adenocarcinoma, TCGA lung adenocarcinoma and TCGA lung cancer databases, the 5-year survival rates of lung cancer patients with high DAPL1 expression (31.9%, 27.5% and 33.0%, respectively) were higher than those with low DAPL1 expression (11.0%, 11.6% and 13.8%, respectively). The differences were statistically significant (P=0.006, 0.028 and 0.025, respectively). The median expression levels of DAPL1 in patients with EGFR Del19 mutation (12.8, 2.75 and 2.9, respectively) were higher than those in patients with other EGFR mutations (11.6, 1.75 and 1.8, respectively, P<0.05). In TCGA lung adenocarcinoma and TCGA lung cancer database, the 5-year survival rate of lung cancer patients with lower DAPL1 methylation levels (22.4% and 16.4%, respectively) were higher than those of lung cancer patients with higher DAPL1 methylation levels (15.1% and 14.2%, respectively), with statistical significance (P<0.05). The expression level of DAPL1 was positively correlated with the EGFR mutant subtype (r=0.909, P<0.05), and negatively correlated with DNA methylation (r=-0.891, P<0.05). The expression of DAPL1 in lung cancer patients was regulated by DNA methylation, which affected the prognosis of lung cancer patients. Conclusion: High DAPL1 expression, or hypomethylation, is associated with lung cancer EGFR Del19 mutation subtype, and DAPL1 hypomethylated lung cancer patients have longer overall survival.目的： 探讨凋亡相关蛋白激酶样蛋白1(DAPL1)低甲基化对表皮生长因子受体19外显子(EGFR Del19)缺失突变型肺癌患者预后的影响。 方法： 收集基因组数据共享(GDC) TCGA肺腺癌、TCGA肺腺癌、TCGA肺癌数据库中肺癌患者的临床病理资料，分析DAPL1甲基化水平对EGFR Del19缺失突变患者预后的影响。相关性分析采用线性回归模型，采用Kaplan-Meier法绘制生存曲线，两组间生存曲线的差异采用Log rank检验。 结果： GDC TCGA肺腺癌、TCGA肺腺癌和TCGA肺癌数据库中，DAPL1高表达肺癌患者的5年生存率(分别为31.9%、27.5%和33.0%)高于DAPL1低表达者(分别为11.0%、11.6%和13.8%)，差异均有统计学意义(P值分别为0.006、0.028和0.025)；EGFR Del19缺失突变亚型肺癌患者的DAPL1中位表达水平(分别为12.8、2.75和2.9)高于EGFR其他亚型突变者(分别为11.6、1.75和1.8，均P<0.05)。TCGA肺腺癌和TCGA肺癌数据库中，DAPL1甲基化水平较低的肺癌患者5年生存率(分别为22.4%和16.4%)高于DAPL1甲基化水平较高的肺癌患者(分别为15.1%和14.2%)，差异均有统计学意义(均P<0.05)。DAPL1表达水平与EGFR突变亚型呈正相关(r＝0.909，P<0.05)，与DNA甲基化呈负相关(r＝-0.891，P<0.05)。肺癌患者DAPL1的表达受DNA甲基化调控，进而影响肺癌患者的预后。 结论： DAPL1的高表达或低甲基化与肺癌EGFR Del19缺失突变亚型有关，DAPL1低甲基化肺癌患者的总生存时间更长。.