Ⅳ期非小细胞肺癌患者外周血Treg细胞与预后相关性分析

Prognostic value of peripheral blood Treg cells in stageⅣnon-small cell lung cancer

目的研究证实肿瘤患者外周血中的免疫细胞亚群对患者疗效预测以及预后判断具有十分重要的价值。本研究旨在探讨驱动基因为阴性的初治Ⅳ期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血T淋巴细胞亚群与其预后关系,寻找有助于其疗效和预后判断的生物学标志物。方法选取2015-09-07-2018-06-28山东省肿瘤医院收治的79例驱动基因为阴性的初治Ⅳ期NSCLC患者为研究对象,收集治疗前3d的外周血并使用流式细胞仪分析外周血中各T淋巴细胞亚群比例。采用Kaplan-Meier生存分析计算患者生存率,Cox比例风险回归分析评估各淋巴细胞亚群以及临床资料特征的潜在预后价值。结果外周血Treg细胞比例低的患者中位无进展生存期(progression free survival,PFS)明显长于比例高的患者(11.0个月vs 6.0个月,P=0.007),同时外周血中Treg细胞比例低的患者中位总生存期(overall survival,OS)也明显长于比例高的患者(27.5个月vs 11.0个月,P=0.003)。除此之外性别也是影响患者PFS的重要因素,女性患者中位PFS明显长于男性患者(16.4个月vs 7.0个月,P=0.010)。单因素分析显示,CD3细胞比例(P=0.027)、Treg细胞比例(P=0.008)、ECOG评分(P=0.017)、肿瘤分化程度(P=0.016)和性别(P=0.013)为影响患者PFS的因素,ECOG评分(P=0.024)、肿瘤分化程度(P=0.024)和Treg细胞比例(P=0.004)为影响患者OS的因素。Cox多因素分析结果显示,外周血中Treg细胞比例的高低(P=0.012)和性别(P=0.012)与患者PFS独立相关,同时外周血中Treg细胞比例高低(P=0.013)也与患者OS独立相关。结论外周血中Treg细胞比例高低是影响驱动基因阴性Ⅳ期NSCLC患者预后的独立因素。

OBJECTIVE A growing number of studies have confirmed that immune cell subsets in peripheral blood of tumor patients have great value in predicting the therapeutic effect and prognosis in patients.This study aimed to explore the relationship between T lymphocyte subtypes and prognosis of patients to identify biomarkers for stageⅣnon-small cell lung cancer(NSCLC).METHODS Totally 79 patients with stageⅣwild type NSCLC from September7 th,2015 to June 28 th,2018 in Shandong Cancer Hospital were collected in our study.The peripheral blood samples of patients were collected 3 days before treatment began,then flow cytometry was used to identify proportions of different lymphocyte subsets.Survival rate was analyzed by Kaplan-meier method.The potential prognostic value of clinicopathologic factors and different T lymphocyte subsets was evaluated by Cox proportional hazards regression.RESULTS Patients with a lower proportion of Treg cells in their peripheral blood had significantly longer median progression free survival(PFS)than patients with a higher proportion of Treg cells(11 months vs 6 months,P=0.007).Meanwhile,the median overall survival(OS)of patients with a lower proportion of Treg cells in their peripheral blood was significantly longer than patients with a high proportion of Treg cells(27.5 months vs 11 months,P=0.003).Furthermore,sex also could affect PFS.Median PFS was significant longer in women than men(16.4 months vs 7 months,P=0.010).Univariate analysis showed that the proportion of CD3 cells(P=0.027),ECOG score(P=0.017),the proportion of Treg cells(P=0.008),tumor differentiation(P=0.016)and sex(P=0.013)were correlated with the PFS of patients.Among which ECOG score(P=0.024),tumor differentiation(P=0.024)and the proportion of Treg cells(P=0.004)were also key factors which could affect the OS of patients.Cox multivariate analysis showed that the proportion of Treg in peripheral blood(P=0.012)and sex(P=0.012)were independently correlated with patient’s PFS,and Treg(P=0.013)was also independently correlated with OS.CONCLUSION The proportion of Treg as an independent factor could predict prognosis of stageⅣwild type NSCLC patient.