PD-L1联合Ki67对非小细胞肺癌不同基因突变情况下分期、预后的影响

Effect of PD-L1 combined with Ki67 on staging and prognosis of non-small cell lung cancer with different gene mutations

目的:探究TP53、EGFR和KRAS突变情况下PD-L1或Ki67异质性表达对非小细胞肺癌患者肿瘤分期分级及预后生存的影响。方法:基于TCGA数据库分析非小细胞肺癌TP53、EGFR和KRAS是否发生突变情况下PD-L1或Ki67表达;qRT-PCR和免疫组化(IHC)验证非小细胞肺癌患者肿瘤组织TP53、EGFR和KRAS突变与否情况下PD-L1或Ki67 mRNA和蛋白水平;TCGA数据分析PD-L1或Ki67异质性表达对患者肿瘤分期的影响,R软件绘制KM生存曲线和DCA曲线验证PD-L1或Ki67异质性表达对非小细胞肺癌TP53、EGFR和KRAS突变患者预后生存及临床模型预测效果的影响。结果:TCGA数据、qRT-PCR和IHC结果表明,TP53突变可导致PD-L1显著上调,而EGFR和KRAS突变后组织PD-L1变化不显著;TP53突变导致Ki67水平显著提高,但EGFR或KRAS突变显著降低Ki67水平;Ki67异质性表达对患者肿瘤分期分级具有显著影响,KM生存曲线表明PD-L1或Ki67异质性表达不影响患者预后,但DCA预测模型中Ki67或Ki67联合PD-L1预测模型的效果更好。结论:Ki67异质性表达显著影响患者肿瘤分期,Ki67或Ki67联合PD-L1预测模型能更好预测患者预后。

Objective:To investigate effects of heterogeneous expression of PD-L1 or Ki67 in mutations of TP53,EGFR and KRAS on tumor staging and prognosis of survival of non-small cell lung cancer patients.Methods:Expressions of PD-L1 and Ki67 with or without TP53,EGFR and KRAS mutations in non-small cell lung cancer were analyzed based on TCGA database.mRNA and protein levels of PD-L1 or Ki67 with or without TP53,EGFR and KRAS mutations were verified by qRT-PCR and immunohistochemis‐try(IHC)in non-small cell lung cancer patient tissues.Effect of heterogeneous expression of PD-L1 or Ki67 on patient tumor staging were analyze by TCGA date,KM survival curves and DCA curves were plotted by R software to verify prognostic survival of non-small cell lung cancer patients with TP53,EGFR and KRAS mutations by heterogeneous expression of PD-L1 or Ki67 and predictive effect of clinical models.Results:TCGA data,qRT-PCR and IHC results showed that TP53 mutation resulted in significant up-regulation of PD-L1,while EGFR and KRAS did not change significantly.TP53 mutation resulted in a significant increase in Ki67 level,EGFR or KRAS mutation significantly decreased Ki67 level.Heterogeneous expression of Ki67 had a significant impact on patient tumor stage grading.KM survival curve indicated that PD-L1 or Ki67 heterogeneous expression did not affect prognostic survival of patients,but DCA prediction model of Ki67 or Ki67 combined with PD-L1 prediction model was more effective.Conclusion:Heterogeneous expres‐sion of Ki67 leads to significant differences in patients'tumor grading stage,and Ki67 or Ki67 combined with PD-L1 prediction model can better predict patients'prognosis.