局部晚期非小细胞肺癌患者KRAS基因突变、程序性死亡受体配体1表达与一线同步放化疗预后的关系

Correlation of KRAS gene mutation and programmed death receptor ligand 1 expression with prognosis of first-line concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer

目的:探讨局部晚期非小细胞肺癌患者KRAS基因突变、程序性死亡受体配体1(PD-L1)表达与一线同步放化疗预后的关系。方法:回顾性分析2018年1月至2021年12月南平市第一医院收治的50例局部晚期非小细胞肺癌患者临床资料,所有患者均接受一线同步放化疗方案治疗,治疗前已获取患者组织标本并石蜡包埋。采用实时荧光定量聚合酶链反应法检测治疗前组织中KRAS基因突变类型,采用免疫组织化学法测定PD-L1表达情况(肿瘤细胞中阳性细胞比例≥1%为阳性),分析KRAS基因状态、PD-L1表达情况与患者临床特征和近期疗效的关系。随访1年,采用Kaplan-Meier法绘制患者无进展生存(PFS)曲线,比较采用log-rank检验。采用单因素和多因素Cox比例风险模型分析患者PFS的影响因素。结果:50例患者中KRAS突变型11例(22.00%),PD-L1阳性36例(72.00%);11例KRAS突变患者中,第2号外显子第13号密码子突变2例、第12号密码子突变9例。患者客观缓解率(ORR)为76.00%(38/50)、临床控制率(DCR)为86.00%(43/50)。KRAS突变型组与KRAS野生型组间患者年龄、病理类型、TNM分期、ORR、DCR差异均无统计学意义(均 P>0.05),KRAS突变型组男性[72.73% (8/11)比38.46%(15/39)]、有吸烟史[90.91%(10/11)比20.51%(8/39)]、PD-L1阳性表达[100.00%(11/11)比64.10%(25/39)]患者比例均高于KRAS野生型组(均 P<0.05);PD-L1阳性组与PD-L1阴性组间患者年龄、病理类型、性别、吸烟史、TNM分期、ORR及DCR差异均无统计学意义(均 P>0.05)。KRAS突变型组和野生型组患者中位PFS时间分别为8.75、11.32个月,两组间PFS差异有统计学意义( P=0.039);PD-L1阳性和阴性患者中位PFS时间分别为10.19、11.16个月,二者间PFS差异无统计学意义( P=0.116)。多因素Cox回归分析显示,KRAS基因突变型为接受一线同步放化疗局部晚期非小细胞肺癌患者PFS的独立危险因素( HR =1.449,95% CI 1.071~1.196, P=0.017),PD-L1表达、吸烟史、性别均不是PFS的独立影响因素(均 P>0.05)。 结论:KRAS基因状态与接受一线同步放化疗治疗的局部晚期非小细胞肺癌患者预后密切相关,而PD-L1表达情况与之无关。

ObjectiveTo investigate the relationship between KRAS gene mutation,programmed death receptor ligand 1(PD-L1)expression and prognosis of first-line concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer.MethodsThe clinical data of 50 patients with locally advanced non-small cell lung cancer who were admitted to Nanping First Hospital from January 2018 to December 2021 were retrospectively analyzed.All patients were treated with first-line concurrent chemoradiotherapy.Tissue samples of patients were obtained and paraffin embedded before treatment.Real-time fluorescence quantitative polymerase chain reaction was used to detect the type of KRAS gene mutation in tissues before treatment,and the expression of PD-L1 was determined by immunohistochemistry(the percentage of positive cells in tumor cells≥1% was positive),and the relationship between KRAS gene status,PD-L1 expression and clinical characteristics and short-term efficacy of patients was analyzed.Patients were followed up for 1 year,and progression-free survival(PFS)curves were plotted by Kaplan-Meier method,and log-rank test was used for comparison.Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of PFS.ResultsAmong the 50 patients,11(22.00%)were KRAS mutant,and 36(72.00%)were PD-L1 positive.Among the 11 patients with KRAS mutation,there were 2 cases of codon 13 mutation and 9 cases of codon 12 mutation in exon 2.The objective response rate(ORR)and clinical control rate(DCR)were 76.00%(38/50)and 86.00%(43/50).There were no significant differences in patients'age,pathological type,TNM stage,ORR and DCR between KRAS mutant group and KRAS wild type group(allP>0.05).The proportions of male patients[72.73%(8/11)vs.38.46%(15/39)],patients with smoking history[90.91%(10/11)vs.20.51%(8/39)]and patients with PD-L1 positive expression[100.00%(11/11)vs.64.10%(25/39)]in KRAS mutant group were higher than those in KRAS wild type group(all P<0.05).There were no significant differences in patients'age,pathological type,gender,smoking history,TNM stage,ORR and DCR between PD-L1 positive group and PD-L1 negative group(all P>0.05).The median PFS time of patients in KRAS mutant group and wild type group was 8.75 and 11.32 months,and the difference in PFS between the two groups was statistically significant(P=0.039).The median PFS time of patients with PD-L1 positive and negative was 10.19 and 11.16 months,and there was no statistical significance in PFS between the two(P=0.116).Multivariate Cox regression analysis showed that KRAS gene mutation was an independent risk factor for PFS in patients with locally advanced NSCLC after first-line concurrent chemoradiotherapy(HR=1.449,95%CI 1.071-1.196,P=0.017).PD-L1 expression,smoking history and gender were not independent influencing factors for PFS(all P>0.05).ConclusionsKRAS gene status is closely related to the prognosis of patients with locally advanced non-small cell lung cancer treated with first-line concurrent chemoradiotherapy,while PD-L1 expression is not.