肺癌合并脓毒症mHLA-DR、CD39<sup>+</sup>Treg及IL-10表达与预后相关性分析

doi:10.3877/cma.j.issn.1674-6902.2023.02.004

目的

分析肺癌合并脓毒症患者中外周单核细胞HLA-DR、外周血CD39⁺ Tregs水平和IL-10表达水平对病情及预后评估的价值。

方法

选择2020年9月至2021年12月我院收治的肺癌合并脓毒症的患者68例，根据其严重程度分为脓毒症组38例，脓毒性休克组30例；同期36例未合并脓毒症的肺癌患者为对照组；测定各组患者入院后外周单核细胞HLA-DR、外周血CD39⁺ Treg及IL-10的水平，分析三种指标与严重程度的相关性，采用ROC曲线分析三种指标及联合检测对脓毒症严重程度和预后评估的能力。

结果

①脓毒症组血清中的CD39⁺ Treg比例、IL-10水平均显著高于对照组(3.92±1.35 vs. 2.14±0.86%)、(37.08±5.32 vs. 9.22±1.75)pg/ml(P<0.01)，mHLA-DR水平在感染前7 d均低于脓毒性休克组和对照组，P<0.01；在入院第7天脓毒症组中HLA-DR降至最低，与入院时水平差异有显著性(91.07±1.14 vs. 84.59±0.7%，P<0.01)；②68例脓毒症肺癌患者中，死亡22例；与生存者相比，死亡者ΔHLA-DR7水平明显降低，CD39⁺ Treg比例、IL-10水平明显升高，P<0.01；③脓毒症组中多因素Logistic回归分析显示ΔHLA-DR7(OR＝2.195，P<0.001)、CD39⁺ Treg(OR＝2.853，P＝0.015)、IL-10(OR＝1.868，P＝0.002)与APACHEⅡ及SOFA评分是脓毒症预后不良的危险因素；④ΔHLA-DR7评价脓毒症预后的曲线下面积为0.911，截断值为8.7%时，敏感度为89.28%，特异度为97.6%，大于CD39⁺ Treg和IL-10，P<0.01；三种指标联合的预后评估能力(曲线下面积为0.925，敏感度为96.61%，特异度为94.32%)明显高于三者的单一检测或两两联合检测。

结论

ΔHLA-DR7是肺癌伴脓毒症严重程度和预后评估的一个良好指标，ΔHLA-DR7与CD39⁺ Treg和IL-10三者联合能够显著提高脓毒症的诊断和预后评估的水平。

关键词: mHLA-DR, CD39⁺ Tregs, 白细胞介素-10, 支气管肺癌, 脓毒症

Objective

To study the value of peripheral monocyte HLA-DR, peripheral blood CD39⁺ Tregs and IL-10 expression in evaluating the state and prognosis of patients with lung cancer complicated with sepsis.

Methods

A total of 68 patients with lung cancer complicated by sepsis who were hospitalized in our hospital from September 2020 to December 2021 were selected and divided into sepsis divided into sepsis group 38 cases, septic shock group 30 cases, lung cancer without sepsis group 36 cases. The levels of mHLA-DR, CD39⁺ Treg and IL-10 in peripheral monocytes were measured after admission. The correlation between the three indexes and the severity was analyzed. ROC curve was used to analyze the three indexes and the ability of combined detection to evaluate the severity and prognosis of sepsis.

Results

① The proportion of CD39⁺ Treg and IL-10 level in lung cancer patients with sepsis were significantly higher than those in non-sepsis group (3.92±1.35 vs. 2.14±0.86%), (37.08±5.32 vs. 9.22±1.75 pg/ml) (P<0.01). The mHLA-DR level was lower than that in non-sepsis group and control group 7 days before infection (P<0.01). HLA-DR decreased to the lowest level in sepsis group on the 7 th day after admission, which was significantly different from that at admission (91.07±1.14 vs. 84.59±0.7%) (P<0.01). The proportion of CD39⁺ Treg and IL-10 levels were higher than those in the survival group (P<0.01); ③Multivariate logistic regression analysis in the lung cancer sepsis group showed that ΔHLA-DR7 (OR=2.195, P<0.001), CD39⁺ Treg (OR=2.853, P=0.015), IL-10 (OR=1.868, P=0.002) and APACHE Ⅱ and SOFA scores were independent risk factors for poor prognosis of sepsis; ④ The area under the curve of ΔHLA-DR7 in evaluating the prognosis of sepsis was 0.911, and when the cutoff value was 8.7%, the sensitivity was 89.28% and the specificity was 97.6%) was greater than that of CD39⁺ Treg and IL-10, and the difference was statistically significant (P<0.01).

Conclusion

ΔHLA-DR 7 is a good index for evaluating the severity and prognosis of lung cancer with sepsis. ΔHLA-DR7 combined with CD39⁺ Treg and IL-10 can significantly improve the diagnosis and prognosis of sepsis.

Key words: mHLA-DR, CD39⁺ Tregs, Interleukin-10, Bronchogenic carcinoma, Sepsis

表1 患者mHLA-DR、CD39⁺ Tregs和IL-10指标比较(±s)

组　别	入院时mHLA-DR	入院第3天mHLA-DR	入院第7天mHLA-DR	mHLA-DR3(%)(第3天-第0日差值)	mHLA-DR7(%)(第7天-第0日差值)	CD39⁺ Tregs(%)	IL-10(pg/ml)
脓毒症组	91.07±1.14^a	87.07±1.22^a	84.59±0.75^ac	4.78±0.61	7.53±1.22^a	3.92±1.35^a	37.08±5.32^a
脓毒症休克组	88.09±1.02^a	84.53±0.98^a	76.24±0.61^ac	6.12±0.49	9.87±1.39^a	5.33±1.81^a	58.76±7.29^ab
对照组	95.07±0.86	94.38±0.99	96.14±1.22	0.96±0.05	0.83±0.08	2.14±0.86	9.22±1.75

表1 患者mHLA-DR、CD39⁺ Tregs和IL-10指标比较(±s)

组　别	入院时mHLA-DR	入院第3天mHLA-DR	入院第7天mHLA-DR	mHLA-DR3(%)(第3天-第0日差值)	mHLA-DR7(%)(第7天-第0日差值)	CD39⁺ Tregs(%)	IL-10(pg/ml)
脓毒症组	91.07±1.14^a	87.07±1.22^a	84.59±0.75^ac	4.78±0.61	7.53±1.22^a	3.92±1.35^a	37.08±5.32^a
脓毒症休克组	88.09±1.02^a	84.53±0.98^a	76.24±0.61^ac	6.12±0.49	9.87±1.39^a	5.33±1.81^a	58.76±7.29^ab
对照组	95.07±0.86	94.38±0.99	96.14±1.22	0.96±0.05	0.83±0.08	2.14±0.86	9.22±1.75

表2 肺癌合并脓毒血症生存者与死亡者指标比较(±s)

临床资料	生存者(n＝46)	死亡者(n＝22)	统计量	P值
年龄(岁)	58.2±6.4	63.9±7.5	2.658	0.266
性别(男/女，n)	21/25	16/6	4.401^c	0.412
脓毒症分级(n)			4.319^a	0.000
脓毒症	30	8
脓毒症休克	8	12
第7天HLA-DR(%)	86.72±0.59	75.69±0.64	17.410	0.010
ΔHLA-DR3(%)	5.89±0.53	6.51±0.40	2.856	0.171
ΔHLA-DR7(%)	7.86±0.47	9.07±0.32	12.115	0.000
CD39⁺ Treg(%)	4.16±1.19	6.08±2.15^b	1.112	0.000
IL-10(pg/ml)	31.39±4.78	62.15±8.34^a	7.319	0.000
APACHEⅡ评分(分)	19.02±4.11	28.56±6.91^b	8.356	0.000
SOFA评分(分)	3.42±1.75	6.63±5.86^a	5.024	0.000

表2 肺癌合并脓毒血症生存者与死亡者指标比较(±s)

临床资料	生存者(n＝46)	死亡者(n＝22)	统计量	P值
年龄(岁)	58.2±6.4	63.9±7.5	2.658	0.266
性别(男/女，n)	21/25	16/6	4.401^c	0.412
脓毒症分级(n)			4.319^a	0.000
脓毒症	30	8
脓毒症休克	8	12
第7天HLA-DR(%)	86.72±0.59	75.69±0.64	17.410	0.010
ΔHLA-DR3(%)	5.89±0.53	6.51±0.40	2.856	0.171
ΔHLA-DR7(%)	7.86±0.47	9.07±0.32	12.115	0.000
CD39⁺ Treg(%)	4.16±1.19	6.08±2.15^b	1.112	0.000
IL-10(pg/ml)	31.39±4.78	62.15±8.34^a	7.319	0.000
APACHEⅡ评分(分)	19.02±4.11	28.56±6.91^b	8.356	0.000
SOFA评分(分)	3.42±1.75	6.63±5.86^a	5.024	0.000

表3 各项指标二元Logistic回归单因素分析

临床资料	估计值	标准误	Wald值	OR值(95%CI)	P值
年龄	0.009	0.012	0.512	1.723(0.549~2.897)	0.012
性别	0.678	0.329	3.162	2.949(0.915~4.982)	0.182
HLA-DR (第0天)	－2.276	1.942	1.374	0.103(0.002~4.616)	0.241
HLA-DR (第3天)	－3.404	2.692	1.599	0.033(0.000~6.502)	0.206
HLA-DR (第7天)	－0.452	1.801	0.063	0.953(0.046~1.859)	0.086
ΔHLA-DR3	1.877	2.261	0.689	0.153(0.02~12.867)	0.406
ΔHLA-DR7	1.658	0.001	14.247	0.169(0.054~0.283)	0.001
CD39⁺ Tregs	0.217	0.045	2.336	1.240(0.941~1.634)	0.006
IL-10	0.164	0.034	3.391	1.068(0.973~1.166)	0.017
APACHEⅡ	0.218	0.042	8.870	2.860(1.693~4.027)	0.000
SOFA	0.674	0.168	15.114	2.008(0.765~3.941)	0.000

表3 各项指标二元Logistic回归单因素分析

临床资料	估计值	标准误	Wald值	OR值(95%CI)	P值
年龄	0.009	0.012	0.512	1.723(0.549~2.897)	0.012
性别	0.678	0.329	3.162	2.949(0.915~4.982)	0.182
HLA-DR (第0天)	－2.276	1.942	1.374	0.103(0.002~4.616)	0.241
HLA-DR (第3天)	－3.404	2.692	1.599	0.033(0.000~6.502)	0.206
HLA-DR (第7天)	－0.452	1.801	0.063	0.953(0.046~1.859)	0.086
ΔHLA-DR3	1.877	2.261	0.689	0.153(0.02~12.867)	0.406
ΔHLA-DR7	1.658	0.001	14.247	0.169(0.054~0.283)	0.001
CD39⁺ Tregs	0.217	0.045	2.336	1.240(0.941~1.634)	0.006
IL-10	0.164	0.034	3.391	1.068(0.973~1.166)	0.017
APACHEⅡ	0.218	0.042	8.870	2.860(1.693~4.027)	0.000
SOFA	0.674	0.168	15.114	2.008(0.765~3.941)	0.000

表4 肺癌伴脓毒症死亡的多因素Logistic回归分析

变　量	估计值	标准误	Wald值	OR值	OR值的95%CI	P值
年龄	0.112	0.326	3.452	1.779	1.082~2.475	0.000
ΔHLA-DR7	0.035	0.010	9.812	2.195	1.046~3.344	0.000
CD39⁺ Treg	1.374	0.028	2.966	2.853	0.959~3.812	0.015
IL-10	0.169	0.201	5.605	1.868	0.917~2.819	0.002
APACHEⅡ	0.152	0.476	7.273	2.379	1.421~3.338	0.000
SOFA	0.063	0.012	8.119	2.163	1.205~3.121	0.000

表4 肺癌伴脓毒症死亡的多因素Logistic回归分析

变　量	估计值	标准误	Wald值	OR值	OR值的95%CI	P值
年龄	0.112	0.326	3.452	1.779	1.082~2.475	0.000
ΔHLA-DR7	0.035	0.010	9.812	2.195	1.046~3.344	0.000
CD39⁺ Treg	1.374	0.028	2.966	2.853	0.959~3.812	0.015
IL-10	0.169	0.201	5.605	1.868	0.917~2.819	0.002
APACHEⅡ	0.152	0.476	7.273	2.379	1.421~3.338	0.000
SOFA	0.063	0.012	8.119	2.163	1.205~3.121	0.000

表5 肺癌合并脓毒症预后评估ROC曲线

指　标	AUC(95%CI)	临界值	敏感度(%)	特异度(%)	约登指数
ΔHLA-DR7(%)	0.911(0.874~0.923)	8.7%	89.28	86.05	0.75
IL-10(pg/ml)	0.816(0.712~0.926)	32.7%	78.62	60.19	0.39
CD39⁺ Treg(%)	0.832(0.755~0.912)	3.6%	80.34	74.72	0.55
mHLA-DR+CD39+Treg	0.918(0.876~0.984)	－	94.15	91.47	0.86
mHLA-DR+IL-10	0.893(0.843~0.957)	－	92.87	90.28	0.83
CD39⁺ Treg+IL-10	0.874(0.827~0.953)	－	91.55	88.69	0.80
mHLA-DR+CD39⁺Treg+IL-10	0.925(0.899~0.996)	－	96.61	94.32	0.91

表5 肺癌合并脓毒症预后评估ROC曲线

指　标	AUC(95%CI)	临界值	敏感度(%)	特异度(%)	约登指数
ΔHLA-DR7(%)	0.911(0.874~0.923)	8.7%	89.28	86.05	0.75
IL-10(pg/ml)	0.816(0.712~0.926)	32.7%	78.62	60.19	0.39
CD39⁺ Treg(%)	0.832(0.755~0.912)	3.6%	80.34	74.72	0.55
mHLA-DR+CD39+Treg	0.918(0.876~0.984)	－	94.15	91.47	0.86
mHLA-DR+IL-10	0.893(0.843~0.957)	－	92.87	90.28	0.83
CD39⁺ Treg+IL-10	0.874(0.827~0.953)	－	91.55	88.69	0.80
mHLA-DR+CD39⁺Treg+IL-10	0.925(0.899~0.996)	－	96.61	94.32	0.91

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Expression of mHLA-DR, CD39⁺ Treg and IL-10 in lung cancer patients with sepsis was correlated with the severity and prognosis of the disease

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Expression of mHLA-DR, CD39+ Treg and IL-10 in lung cancer patients with sepsis was correlated with the severity and prognosis of the disease

Expression of mHLA-DR, CD39⁺ Treg and IL-10 in lung cancer patients with sepsis was correlated with the severity and prognosis of the disease