培美曲塞联合顺铂一线化疗方案治疗肺腺癌生存预测中T淋巴细胞亚群基线水平的价值评估

Value Evaluation of T Lymphocyte Subsets Baseline Level in the Survival Prediction of Lung Adenocarcinoma Treated with Pemetrexed Combined with Cisplatin as First-Line Chemotherapy Regimen

目的探讨T淋巴细胞亚群基线水平在培美曲塞联合顺铂一线化疗方案治疗肺腺癌生存预测中的价值。方法选取医院呼吸科2015年1月至2019年12月接受培美曲塞联合顺铂一线化疗方案治疗的肺腺癌患者147例,按不同化疗疗效分为完全缓解(CR)+部分缓解(PR)组(61例)、疾病稳定(SD)组(56例)和疾病进展(PD)组(30例)。采用LSD-t检验或χ^(2)检验分析肺腺癌患者外周血T淋巴细胞亚群基线水平与临床病理特征的关系,进一步比较不同化疗疗效患者的T淋巴细胞亚群基线水平,采用Cox回归分析评价CD_(8)^(+)T细胞比例和CD_(4)^(+)/CD_(8)^(+)基线水平对肺腺癌患者化疗后2年总生存率(OS)的影响,采用Kaplan-Meier生存分析分别比较CD_(8)^(+)≥32.0%和CD_(8)^(+)<32.0%,CD_(4)^(+)/CD_(8)^(+)>1.3和CD_(4)^(+)/CD_(8)^(+)≤1.3两组肺腺癌患者化疗后6个月、1年、2年的OS。结果CD_(8)^(+)T细胞比例和CD_(4)/CD_(8)^(+)与肺腺癌患者淋巴结转移、TNM/T分期和远处转移密切相关(P<0.05)。CR+PR组的CD_(8)^(+)T细胞比例基线水平为(36.5±8.1)%,显著高于SD组的(31.2±6.9)%及PD组的(29.5±7.4)%(P<0.05);CR+PR组的CD_(4)^(+)/CD_(8)^(+)基线水平为1.1±0.3,显著低于SD组的1.5±0.4及PD组的1.6±0.4(P<0.05)。多因素Cox回归分析显示,CD_(8)^(+)T细胞比例和CD_(4)^(+)/CD_(8)^(+)基线水平均为影响肺腺癌患者化疗后2年OS[HR=1.56,95%CI(1.15,3.98),P=0.028;HR=1.67,95%CI(1.35,4.24),P=0.039]的独立预测因素。Kaplan-Meier生存分析结果显示,CD_(8)^(+)≥32.0%和CD_(4)^(+)/CD_(8)^(+)≤1.3的患者化疗后6个月、1年、2年OS均显著高于CD_(8)^(+)<32.0%和CD_(4)^(+)/CD_(8)^(+)>1.3的患者(100.00%比91.44%、89.53%比65.43%、72.32%比45.61%,100.00%比93.63%、92.53%比60.92%、78.61%比44.53%,P<0.05)。结论外周血CD_(8)^(+)T细胞比例基线水平较高、CD_(4)^(+)/CD_(8)^(+)基线水平较低,提示患者化疗后生存时间较长,预后较好。

Objective To investigate the value of T lymphocyte subsets baseline level in the survival prediction of lung adenocarcinoma treated with pemetrexed combined with cisplatin as first-line chemotherapy regimen.Methods A total of 147 patients with lung adenocarcinoma who received pemetrexed combined with cisplatin as first-line chemotherapy regimen in the Department of Respiratory of the hospital from January 2015 to December 2019 were selected and divided into the complete remission(CR)+partial remission(PR)group(61 cases),stable disease(SD)group(56 cases)and disease progression(PD)group(30 cases)according to the different chemotherapy efficacy.LSD-t test orχ^(2) test was used to analyze the relationship between the baseline level of peripheral blood T lymphocyte subsets and clinicopathological characteristics in patients with lung adenocarcinoma,and to further compare the baseline levels of T lymphocyte subsets in patients with different chemotherapy efficacy.Cox regression analysis was used to evaluate effects of CD_(8)^(+)T cell ratio and CD_(4)^(+)/CD_(8)^(+) baseline level on 2-year overall survival(OS)rate in patients with lung adenocarcinoma after chemotherapy.Kaplan-Meier survival analysis was used to compare the 6-month,1-year,and 2-year OS in patients with lung adenocarcinoma in CD_(8)^(+)≥32.0%and CD_(8)^(+)<32.0%group,CD_(4)^(+)/CD_(8)^(+)>1.3 and CD_(4)^(+)/CD_(8)^(+)≤1.3 group.Results CD_(8)^(+)T cell ratio and CD_(4)^(+)/CD_(8)^(+) were associated with lymph node metastasis,TNM/T stage and distant metastasis in patients with lung adenocarcinoma(P<0.05).The baseline level of CD_(8)^(+)T cells ratio in the CR+PR group was(36.5±8.1)%,which was significantly higher than(31.2±6.9)%in the SD group and(29.5±7.4)%in the PD group(P<0.05).The baseline level of CD_(4)^(+)/CD_(8)^(+)in the CR+PR group was 1.1±0.3,which was significantly lower than 1.5±0.4 in the SD group and 1.6±0.4 in the PD group(P<0.05).Multivariate Cox regression analysis showed that CD_(8)^(+)T cell ratio and CD_(4)^(+)/CD_(8)^(+) baseline level were independent predictors of 2-year OS[HR=1.56,95%CI(1.15,3.98),P=0.028;HR=1.67,95%CI(1.35,4.24),P=0.039]in patients with lung adenocarcinoma after chemotherapy.Kaplan-Meier survival analysis showed that the 6-month,1-year,and 2-year OS after chemotherapy in patients with CD_(8)^(+)≥32.0%and CD_(4)^(+)/CD_(8)^(+)≤1.3 were significantly higher than those of patients with CD_(8)^(+)<32.0%and CD_(4)^(+)/CD_(8)^(+)>1.3(100.00%vs.91.44%,89.53%vs.65.43%,72.32%vs.45.61%and 100.00%vs.93.63%,92.53%vs.60.92%,78.61%vs.44.53%,P<0.05).Conclusion The baseline level of CD_(8)^(+)T cell ratio is higher,while the baseline level of CD_(4)^(+)/CD_(8)^(+) is lower in peripheral blood,which suggests that patients have longer survival time and better prognosis after chemotherapy.