切换至 "中华医学电子期刊资源库"

中华肺部疾病杂志(电子版) ›› 2023, Vol. 16 ›› Issue (02) : 169 -174. doi: 10.3877/cma.j.issn.1674-6902.2023.02.004

论著

肺癌合并脓毒症mHLA-DR、CD39+Treg及IL-10表达与预后相关性分析
张宁1, 周明明1,(), 蒋正英1, 吴桂新1, 吕奇坤1   
  1. 1. 400030 重庆,重庆大学附属肿瘤医院
  • 收稿日期:2022-11-29 出版日期:2023-04-25
  • 通信作者: 周明明
  • 基金资助:
    重庆市医学科卫联合科研项目(2020FYYX173)

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

Ning Zhang1, Mingming Zhou1,(), Zhengying Jiang1, Guixin Wu1, Qikun Lyu1   

  1. 1. Department of Critical Care Medicine, Chongqing University Cancer Hospital, Chongqing 400030, China
  • Received:2022-11-29 Published:2023-04-25
  • Corresponding author: Mingming Zhou
引用本文:

张宁, 周明明, 蒋正英, 吴桂新, 吕奇坤. 肺癌合并脓毒症mHLA-DR、CD39+Treg及IL-10表达与预后相关性分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(02): 169-174.

Ning Zhang, Mingming Zhou, Zhengying Jiang, Guixin Wu, Qikun Lyu. 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[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(02): 169-174.

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。

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.

表1 患者mHLA-DR、CD39+ Tregs和IL-10指标比较(±s)
表2 肺癌合并脓毒血症生存者与死亡者指标比较(±s)
表3 各项指标二元Logistic回归单因素分析
表4 肺癌伴脓毒症死亡的多因素Logistic回归分析
表5 肺癌合并脓毒症预后评估ROC曲线
1
Taccone FS, Artigas AA, Sprung CL, et al. Characteristics and outcomes of cancer patients in European ICUs[J]. Crit Care, 2009, 13(1): R15.
2
Vandijck DM, Benoit DD, Depuydt PO, et al. Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic patients with cancer and sepsis 307 shock patients with hematological malignancies[J]. Intensive Care Med, 2008, 34(5): 847-855.
3
Hampshire PA, Welch CA, McCrossan LA, et al. Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database[J]. Crit Care, 2009, 13(4): R137.
4
Tolsma V, Schwebel C, Azoulay E, et al. Sepsis severe or septic shock: outcome according to immune status and immunodeficiency profile[J]. Chest, 2014, 146(5): 1205-1213.
5
Yin J, Chen Y, Huang JL, et al. Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study[J].World J Emerg Med, 2021, 12(3): 185-191.
6
Vuk-Pavlovic S. Rebuilding immunity in cancer patients[J]. Blood Cells Mol Dis, 2008, 40(1): 94-100.
7
Zanza C, Caputo G, Tornatore G, et al. Cellular immuno-profile in septic human host: A scoping review[J]. Biology (Basel), 2022, 11(11): 1626.
8
Mirouse A, Vigneron C, Llitjos JF, et al. Sepsis and cancer: An interplay of friends and foes[J]. Am J Respir Crit Care Med, 2020, 202(12): 1625-1635.
9
Peters van Ton AM, Kox M, Abdo WF, et al. Precision immunotherapy for sepsis[J]. Front Immunol, 2018, 9: 1926.
10
Fumeaux T, Pugin J. Is the measurement of monocytes HLA-DR expression useful in patient with sepsis[J]. Intensive Care Med, 2006, 32(8): 1106-1108.
11
Zhuang YG, Peng H, Chen YZ, et al. Dynamic monitoring of monocyte HLA-DR expression for the diagnosis, prognosis, and prediction of sepsis[J]. Front Biosci (Landmark Ed), 2017, 22(8): 1344-1354.
12
Tschaikowsky K, Hedwig-Geissing M, Schiele A, et al. Coincidence of pro- and anti-inflammatory responses in the early phase of severe sepsis: Longitudinal study of mononuclear histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in septic and postoperative patients[J]. Crit Care Med, 2002, 30(5): 1015-1023.
13
Le Tulzo Y, Pangault C, Amiot L, et al. Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock[J]. Am J Respir Crit Care Med, 2004, 169(10): 1144-1151.
14
Pangault C, Le Tulzo Y, Tattevin P, et al. Down-modulation of granulocyte macrophage-colony stimulating factor receptor on monocytes during human septic shock[J]. Rit Care Med, 2006, 34(4): 1193-1201.
15
Winkler MS, Rissiek A, Priefler M, et al. Human leucocyte antigen (HLA-DR) gene expression is reducedin sepsis and correlates with impaired TNF-αresponse: A diagnostic tool for immunosuppression?[J]. PLoS One, 2017, 12(8): e0182427.
16
Becker C, Kubach J, Wijdenes J, et al. CD4-mediated functional activation of human CD4+CD25+ regulatory T cells[J]. Eur J Immunol, 2007, 37(5): 1217-1223.
17
Wachstein J, Tischer S, Figueiredo C, et al. HSP70 enhances immunosuppressive function of CD4(+)CD25(+)FoxP3(+) T regulatory cells and cytotoxicity in CD4(+)CD25(-) T cells[J]. PLoS One, 2012, 7(12): e51747.
18
Wang L, Xie Y, Zhu LJ, et al. An association between immunosenescence and CD4(+)CD25(+) regulatory T cells: a systematic review[J]. Biomed Environ Sci, 2010, 23(4): 327-232.
19
Tiemessen MM, Jagger AL, Evans HG, et al. CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages[J]. Proc Natl Acad Sci U S A, 2007, 104(49): 19446-19451.
20
Borsellino G, Kleinewietfeld M, DiMitri D, et al. Expression of ectonucleotidase CD39 by Foxp3+Treg cells: hydrolysis of extracellular ATP and immune suppression[J]. Blood, 2007, 110(4): 1225-1232.
21
Liu J, Shi K, Chen M, et al. Elevated miR-155 expression induces immunosuppression via CD39(+) regulatory T-cells in sepsis patient[J]. Int J Infect Dis, 2015, 40: 135-141.
22
Huang H, Xu R, Lin F, et al. Highcirculating CD39(+) regulatory T cells predict poorsurvival for sepsis patients[J]. Int J Infect Dis, 2015, 30: 57-63.
23
Dimitrov E, Enchev E, Minkov G, et al. Outcome could be predicted by lower monocyte human leukocyte antigen-DR expression in patients with complicated intra-abdominal infections: A review. [J]. Surg Infect, 2020, 21(2): 77-80.
24
Mokart D, Textoris J, Chow-Chine L, et al. HLA-DR and B7-2 (CD86) monocyte expressions after major cancer surgery: profile in sepsis[J]. Minerva Anestesiol, 2011, 77(5): 522-527.
25
Li L, Chen L, Lin F, et al. Study of the expression of inflammatory factors IL-4, IL-6, IL-10, and IL-17 in liver failure complicated by coagulation dysfunction and sepsis[J]. J Inflamm Res, 2021, 14: 1447-1453.
26
Gogos CA, Drosou E, Bassaris HP, et al. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options[J]. J Infect Dis, 2000, 181(1): 176-180.
27
Zhang W, Wang W, Hou W, et al. The diagnostic utility of IL-10, IL-17, and PCT in patients with sepsis infection[J]. Front Public Health, 2022, 10: 923457.
28
Hynninen M, Pettil V, Takkunen O, et al. Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and -10 levels in critically ill patients with sepsis[J]. Shock, 2003, 20(1): 1-4.
29
Wang S, Li T, Li Y, et al. Predictive value of four different scoring systems for septic patient′s outcome: a retrospective analysis with 311 patients[J]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 2017, 29(2): 133-138.
30
Nathan N, Sculier JP, Ameye L, et al. Sepsis and septic shock definitions in patients with cancer admitted in ICU[J]. J Intensive Care Med, 2021, 36(3): 255-261.
[1] 韩媛媛, 热孜亚·萨贝提, 冒智捷, 穆福娜依·艾尔肯, 陆晨, 桑晓红, 阿尔曼·木拉提, 张丽. 组合式血液净化治疗对脓毒症患者血清炎症因子水平和临床预后的影响[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 272-278.
[2] 孟建标, 张庚, 焦燕娜. 脓毒症合并心功能障碍患者早期肠道微生态改变的探讨[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 279-285.
[3] 陈宇, 冯芳, 张露, 刘健. 基于生物信息学分析筛选脓毒症心肌病关键致病基因[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 286-291.
[4] 莫小乔, 胡喆莹, 廖冬花, 谢天. 脓毒症继发急性肾损伤患者死亡风险预测模型构建及评估[J]. 中华危重症医学杂志(电子版), 2023, 16(03): 198-206.
[5] 张晓燕, 肖东琼, 高沪, 陈琳, 唐发娟, 李熙鸿. 转录因子12过表达对脓毒症相关性脑病大鼠大脑皮质的保护作用及其机制[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 540-549.
[6] 魏徐, 张鸽, 伍金林. 新生儿脓毒症相关性凝血病的监测和治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 379-386.
[7] 姚咏明. 如何精准评估烧伤脓毒症患者免疫状态[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 552-552.
[8] 窦上文, 邓欢, 刘邦锋, 岳高远志, 朱华财, 刘永达. 术前复查尿培养在预测微通道经皮肾镜取石术相关感染并发症中的作用[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 361-366.
[9] 梁开地, 缑文斌, 莫居容. 肺癌组织中细胞角蛋白18的表达及与预后的相关性[J]. 中华肺部疾病杂志(电子版), 2023, 16(05): 688-690.
[10] 李伟, 卓剑, 黄川, 黄有攀. Lac、HO-1、sRAGE、CRP/ALB表达及脓毒症并发ARDS危险因素分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 514-516.
[11] 蒙姣姣, 胡刚, 欧阳涣堃. 肺癌术前淋巴结转移及MWA手术效果预测分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 547-549.
[12] 王玉琳, 孙晓容. 晚期肺癌大咯血输注垂体后叶素渗漏救治成功一例[J]. 中华肺部疾病杂志(电子版), 2023, 16(03): 451-452.
[13] 苗软昕, 乔晞. Toll样受体在脓毒症性急性肾损伤中的作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 210-214.
[14] 谭睿, 王晶, 於江泉, 郑瑞强. 脓毒症中高密度脂蛋白、载脂蛋白A-I和血清淀粉样蛋白A的作用研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(06): 749-753.
[15] 蔡荇, 郑瑞强. 肝素结合蛋白在脓毒症中的应用及研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(04): 487-490.
阅读次数
全文


摘要