新辅助化疗对AEG患者手术疗效及CD66b^(+)中性粒细胞、Treg细胞和Breg细胞比例的影响

Effect of neoadjuvant chemotherapy on surgical efficacy and the proportion of CD66b^(+)neutrophils,Treg cells and Breg cells in patients with AEG

目的分析新辅助化疗对食管胃结合部腺癌(adenocarcinoma of esophagogastric junction,AEG)患者疗效及CD66b^(+)中性粒细胞、调节性T细胞(regulatory cell,Treg)和调节性B细胞(regulatory B cell,Breg)水平的影响。方法收集2018年1月至2019年6月海安市人民医院经胃镜病理活检诊断的122例Ⅱ-Ⅲ期AEG手术患者为研究对象,单纯手术治疗者设为对照组(63例),联合新辅助化疗者为实验组(59例)。采用卡式功能(Karnofsky,KPS)评分评价治疗效果;免疫组织化学染色对肿瘤病灶的CD66b^(+)中性粒细胞进行计数;流式细胞仪检测Treg、Breg及CD3^(+)、CD4^(+)、CD8^(+)细胞水平,根据随访结果分析患者生存情况,采用Spearman相关性分析患者的生存状况与肿瘤组织Treg细胞、Breg细胞、CD66b^(+)中性粒细胞的相关性,统计治疗期间患者不良反应发生情况。结果经过治疗后,实验组和对照组KPS评分均升高,且实验组KPS评分高于对照组,差异具有统计学意义[分:(85.59±1.27)比(82.33±1.33),t=13.85,P<0.05)];实验组CD66b^(+)中性粒细胞计数低于对照组[109/L:(5.66±1.47)比(8.75±1.15),t=12.87,P<0.05)];实验组和对照组患者的Treg细胞和Breg细胞比例均下降,且实验组患者的Treg细胞和Breg细胞低于对照组[%:(2.05±0.21)比(3.11±0.23);(3.05±0.80)比(4.68±0.76),t值分别为26.61和11.52,P值均<0.05)];实验组肿瘤组织的CD3^(+)、CD4^(+)细胞水平高于对照组,CD8^(+)细胞低于对照组,差异均具有统计学意义[%:(0.99±0.21)比(0.78±0.12),(0.68±0.23)比(0.37±0.09),(0.44±0.04)比(0.64±0.12),t值分别为6.72、9.68和12.51,P值均<0.05)];实验组患者中位总生存期(overall survival,OS)、无进展生存期(progression-free survival,PFS)均高于对照组[月:(12.77±2.08)比(10.04±2.01),(9.62±1.24)比(7.43±1.11),t值分别为34.34、10.25,P值均<0.05)];实验组和对照组患者不良反应发生率的差异无统计学意义(P>0.05)。结论AEG患者术前采用新辅助化疗较对照组CD66b^(+)中性粒细胞、Treg细胞和Breg细胞比例降低,治疗效果良好,建议推广。

Objective To analyze the effect of neoadjuvant chemotherapy on the efficacy of adenocarcinoma of esophagogastric junction(AEG)patients and the levels of CD66b^(+)neutrophils,regulatory cell(Treg)and regulatory B cell(Breg).Methods A total of 122 patients with stage Ⅱ-Ⅲ AEG diagnosed by gastroscope pathological biopsy in Hai'an People's Hospital from January 2018 to June 2019 were selected as the research object,the patients with simple surgical treatment were set as the control group(63 cases),and those with neoadjuvant chemotherapy were set as the experimental group(59 cases).The Karnofsky(KPS)score was used to evaluate treatment effectiveness.Immunohistochemical staining was used to count CD66b^(+)neutrophils in tumor lesions.Flow cytometry was used to detect the proportion of Treg,Breg,and CD3^(+),CD4^(+),and CD8^(+)cells in patients.The patient's survival status was analyzed based on follow-up results,and Spearman correlation analysis was used to analyze the correlation between the patient's survival status and Treg cells,Breg cells,and CD66b^(+)neutrophils of tumor tissue.The incidence of adverse reactions in patients during treatment was counted.Results After treatment,the Karnofsky(KPS)scores of the two groups were increased,and the KPS scores of the experimental group were significantly higher than control group[points:(85.59±1.27)vs(82.33±1.33),t value was 13.85,P<0.05)].The CD66b^(+)neutrophil count in the experimental group was lower than in the control group[109/L:(5.66±1.47)vs(8.75±1.15),t value was 12.87,P<0.05)].The proportion of Treg cells and Breg cells in the two groups was decreased,and the proportion of Treg cells and Breg cells in the experimental group was significantly lower than that in the control group[%:(2.05±0.21)vs(3.11±0.23),(3.05±0.80)vs(4.68±0.76),t values were 26.61 and 11.52,respectively,both P values<0.05)].The proportion of CD3^(+)and CD4^(+)cells in the tumor tissue of the experimental group was higher than that of the control group,while the proportion of CD8^(+)cells was lower than that of the control group[%:(0.99±0.21)vs(0.78±0.12),(0.68±0.23)vs(0.37±0.09),(0.44±0.04)vs(0.64±0.12),t values were 6.72,9.68 and 12.51,respectively,all P values<0.05].Median overall survival(OS),and progression-free survival(PFS)were higher in the experimental group than those in the control group[months:(12.77±2.08)vs(10.04±2.01),(9.62±1.24)vs(7.43±1.11),t values were 34.34 and 10.25 both P values<0.05)].There was no statistically significant difference in the incidence of adverse reactions between the experimental group and the control group(P>0.05).Conclusion After preoperative neoadjuvant chemotherapy,the proportion of CD66b^(+)neutrophils,Treg cells,and Breg cells in AEG patients are significantly lower than those in the control group.The treatment has achieved good results and is worth promoting.