肺磨玻璃结节患者血清炎症因子及髓源性抑制细胞的表达水平及临床意义

郭婧瑶; 骆莹滨; 吴建春; 张博; 李雁

doi:10.12354/j.issn.1000-8179.2022.20220275

肺磨玻璃结节患者血清炎症因子及髓源性抑制细胞的表达水平及临床意义

doi: 10.12354/j.issn.1000-8179.2022.20220275

郭婧瑶^{1, 2,},
骆莹滨²,
吴建春²,
张博²,
李雁^2, ,

1.
上海中医药大学（上海市200071）
2.
上海中医药大学附属市中医医院肿瘤科

基金项目: 本文受国家自然基金面上项目（编号：81973795）和上海申康三年行动计划项目（编号：SHDC2020CR4052）赞助

详细信息

作者简介:
郭婧瑶：专业方向为中医药防治恶性肿瘤的机制及临床研究

通讯作者:
李雁 yan.xiaotian@shutcm.edu.cn

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出版历程
- 收稿日期: 2022-02-21
- 录用日期: 2022-04-01
- 网络出版日期: 2022-04-15

Expression levels and clinical significance of serum inflammatory cytokines andmyeloid-derived suppressor cells in patients with pulmonary ground-glass nodule

Jingyao Guo^{1, 2
,},
Yingbin Luo²,
Jianchun Wu²,
Bo Zhang²,
Yan Li^{2
, ,}

1.
Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
2.
Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200071, China

Funds: This work was supported by the National Natural Foundation of China (No. 81973795) and Three-Year Action Plan of Shanghai Shenkang Hospital Development Center (No. SHDC2020CR4052)

More Information

Corresponding author: Yan Li; E-mail: yan.xiaotian@shutcm.edu.cn

摘要

摘要: 目的探究血清炎症因子及外周血髓源性抑制细胞（myeloid-derived suppressor cells，MDSCs）在直径≤1 cm的肺磨玻璃结节（ground-glass nodule，GGN）患者中的表达，分析可能影响肺结节大小及进展的临床指标和意义。方法采用前瞻性研究方法纳入2020年4月至2021年7月就诊于上海中医药大学附属市中医医院肺GGN直径≤1 cm的患者111例，根据肺结节大小分为微小结节组（直径<5 mm）、小结节组（直径为5～10 mm），其中微小结节组36例，小结节组75例。检测各组患者血清炎症因子表达以及外周血髓源性抑制细胞的比例，分析组间差异。后续每半年随访1次，以影像学显示肺GGN直径增大2 mm及以上或出现新的GGN为研究终点，分析可能影响肺GGN进展的危险因素。结果小结节组较微小结节组患者MDSCs的比例升高，差异具有统计学意义（P<0.05），两组间炎症因子白细胞介素-2（interleukin-2，IL-2）、白细胞介素-6（interleukin-6，IL-6）、白细胞介素-8（interleukin-8，IL-8）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）表达差异无统计学意义（P>0.05）。两组间肺结节变化率差异无统计学意义（P>0.05）。MDSCs是影响肺GGN进展的危险因素，差异具有统计学意义（P<0.05），根据MDSCs表达水平的截断值进行分组分析，结果显示MDSCs低水平表达组（MDSCs<4.57%）较高水平表达组（MDSCs≥4.57%）疾病稳定期更长，差异具有统计学意义（P=0.001）。结论 MDSCs表达水平与肺GGN大小相关，可能是影响肺GGN进展的因素之一。
- 肺结节 /
- 磨玻璃结节 /
- 炎症因子 /
- 髓源性抑制细胞 /
- 临床观察
Abstract: Objective To assess the expression of serum inflammatory cytokines and proportion of peripheral blood myeloid-derived suppressor cells (MDSCs) in patients with ground-glass nodule (GGN) ≤1 cm in diameter and analyze clinical indicators that may affect the size and progression of pulmonary nodules and their clinical significance. Methods This prospective study included 111 patients with pulmonary GGNs ≤1 cm in diameter who were admitted to Shanghai Municipal Hospital of Traditional Chinese Medicine from April 2020 to July 2021. Based on pulmonary nodule size, 36 and 75 patients were assigned into minute nodule (diameter <5 mm) and small nodule (diameter 5–10 mm) groups, respectively. The expression of inflammatory cytokines and proportion of MDSCs were determined, and the differences between the groups were analyzed. Follow-up visits were conducted every 6 months. The study endpoint was an increase in pulmonary GGN diameter of ≥2 mm or the occurrence of new GGNs. Risk factors that could affect the progression of pulmonary GGNs were also analyzed. Results The proportion of MDSCs was higher in the small nodule group than in the minute nodule group, with the difference being significant (P<0.05). Interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) expressions were not significantly different between the two groups (P>0.05). There was no significant difference in the change rate of pulmonary nodules between the two groups (P>0.05). The proportion of MDSCs was a risk factor that affected the progression of pulmonary GGNs, and the difference was statistically significant (P<0.05). Based on the cutoff proportion of MDSCs, the duration of stable disease stage was longer in the low-proportion MDSCs group (MDSCs <4.57%) than in the high-proportion MDSCs expression group (MDSCs≥4.57%), and the difference was statistically significant (P=0.001). Conclusions The proportion of MDSCs is correlated with the size of pulmonary GGNs, which may be one of the factors affecting the progression of pulmonary GGNs.
- pulmonary nodules /
- ground-glass nodule (GGN) /
- inflammatory cytokines /
- myeloid-derived suppressor cells (MDSCs) /
- clinical observation

HTML全文

图 1 流式细胞术检测两组间MDSCs百分比

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图 2 MDSCs百分比与结局指标ROC曲线分析

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图 3 不同MDSCs水平患者疾病稳定期的K-M曲线

下载: 全尺寸图片幻灯片

表 1 两组患者一般临床资料比较

项目	微小结节组（n=36）	小结节组（n=75）	χ²/F	P
性别			0.405^a	0.527
男	11	29
女	25	46
年龄（岁）	54.17±14.49	55.40±13.17	1.628^b	0.205
吸烟史			0.936^a	−
有	5	10
无	31	65
家族史			0.929^a	1.000
有	6	12
无	30	63
结节数量			0.116^a	0.137
孤立性	16	22
多发性	20	53
^a：χ²值，^b：F值

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表 2 两组间炎症因子及MDSCs表达水平比较

项目	微小结节组（n=36）	小结节组（n=75）	F/Z	P
IL-2	333.89±105.68	322.80±100.28	0.112^b	0.593
IL-6	1.52（1.09）	2.08（1.30）	−1.603^c	0.109
IL-8	8.30（6.10）	7.27（4.76）	−0.624^c	0.533
TNF-α	6.15（3.72）	5.88（2.00）	−1.841^c	0.066
MDSCs（%）	2.56（2.50）	3.63（5.44）	−1.997^c	0.046
^b：F值，^c：Z值

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表 3 两组间肺GGN变化率比较

结节变化	微小结节组（n=36）	小结节组（n=75）	P
稳定	33（8.33）	68（9.33）	0.585
增大/增多	3（91.67）	7（90.67）	−
（）内单位为%

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表 4 肺GGN单因素分析

参数	结节稳定	结节增大	OR	95%CI		P
参数	结节稳定	结节增大	OR	下限	上限	P
结节大小（mm）			1.132	0.275	4.661	0.863
<5	33（91.67）	3（8.33）
5～10	68（90.67）	7（9.33）
结节数量			0.451	0.091	2.24	0.331
孤立性	36（89.74）	2（5.26）
多发性	65（89.00）	8（11.00）
吸烟史			1.692	0.323	8.859	0.533
否	88（91.67）	8（8.33）
是	13（86.67）	2（13.33）
家族史			0.549	0.065	4.623	0.581
否	84（90.32）	9（9.68）
是	17（94.44）	1（5.56）
IL-2	−	−	0.975	0.948	1.004	0.086
IL-6	−	−	0.806	0.432	1.503	0.497
IL-8	−	−	0.877	0.672	1.143	0.331
TNF-α	−	−	2.065	0.666	6.409	0.209
MDSCs（%）	−	−	1.728	1.009	2.957	0.046
（）内单位为%

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表 5 不同MDSCs表达水平对肺GGN进展的影响分析

MDSCs分组	疾病稳定期（月）	χ²	P
低水平表达组	20.565±0.303	11.372	0.001
高水平表达组	17.075±0.907	−	−

下载: 导出CSV

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