目的: 探究微小RNA-133（microRNA133,miR-133）、C反应蛋白（C-reactive protein,CRP）、T细胞免疫球蛋白及黏蛋白域蛋白4（T-cell immunoglobulin and mucin domain 4,TIM-4）与肺部感染病情分级及生存结局之间关联性,为临床诊疗提供参考。方法: 选取2020年5月―2023年5月宁夏宝石花医院收治的200例肺部感染患者,进行感染分级[肺炎严重程度指数（PSI）评分Ⅰ~Ⅲ级组（85例）、PSI评分Ⅳ级（81例）、PSI评分Ⅴ级组（34例）],分析各组外周血miR-133、CRP、TIM-4表达,并根据28 d生存状况将肺部感染患者分为存活亚组及病亡亚组,比较每组内两个亚组外周血各指标表达,并分析外周血miR-133、CRP、TIM-4与肺部感染病情分级及生存结局的关系。结果: ①不同时间点间的外周血miR-133、CRP、TIM-4表达均有差别。②存活组与病亡组的外周血miR-133、CRP、TIM-4表达有差别,存活组与病亡组相比外周血miR-133、CRP、TIM-4表达水平较低。③存活组与病亡组的外周血miR-133、CRP、TIM-4表达水平变化趋势有差别;入院后3 d外周血miR-133水平（OR=1.445,95%CI：1.037-2.014）、CRP水平（OR=1.534,95%CI：1.082-2.174）、TIM-4水平（OR=1.516,95%CI：1.086-2.116）、入院后7 d外周血miR-133水平（OR=1.550,95%CI：1.125-2.136）、CRP水平（OR=1.649,95%CI：1.213-2.241）和TIM-4水平（OR=1.609,95%CI：1.175-2.202）均为肺部感染患者病亡的危险因素（P<0.05）。入院当日外周血miR-133水平（rs=0.645,P<0.001）、CRP（rs=0.726,P<0.001）、TIM-4（rs=0.671,P<0.001）与肺部感染病情分级均呈正相关。入院后3 d各指标联合预测的AUC为0.941,敏感度为92.59%,特异度为87.86%;入院后7 d各指标联合预测的AUC为0.952,敏感度为88.89%,特异度为95.38%。结论: 外周血miR-133、CRP、TIM-4表达水平与肺部感染病情分级呈正相关,三者联合预测肺部感染患者生存状况有较高效能,高水平miR-133、CRP、TIM-4的肺部感染患者病亡风险较高,监测miR-133、CRP、TIM-4可为临床诊疗与预后评估提供指导。
Abstract
Objective To explore the association between microRNA133(miR-133), C-reactive protein (CRP), T-cell immunoglobulin and mucin domain 4(TIM-4) and the severity and survival outcomes of lung infections, and to provide a reference for clinical diagnosis and treatment. Methods A total of 200 patients with lung infection admitted to Ningxia Baoshihua Hospital from May 2020 to May 2023 were selected for infection classification [pneumonia severity index (PSI) score group I-III (85 cases), PSI score group IV (81 cases), PSI score group V (34 cases) ]. The expression of miR-133, CRP, and TIM-4 in peripheral blood of each group was analyzed. According to the 28-day survival status, the lung infection patients were divided into survival subgroup and death subgroup. The expression of each index in peripheral blood of the two subgroups in each group was compared, and the relationship between miR-133, CRP, and TIM-4 in peripheral blood, lung infection severity, and survival outcome was analyzed. Results ① There were differences in the expression levels of miR-133, CRP, and TIM-4 in peripheral blood at different time points. ② There were differences in the expression levels of miR-133, CRP, and TIM-4 in peripheral blood between the survival group and the death group, and the expression levels of miR-133, CRP, and TIM-4 in peripheral blood were lower in the survival group compared with the death group. ③ There were differences in the trends of changes in the expression levels of miR-133, CRP, and TIM-4 in peripheral blood between the survival group and the death group. Three days after admission, the levels of miR-133(OR=1.445, 95%CI: 1.037-2.014), CRP (OR=1.534, 95%CI: 1.082-2.174), and TIM-4(OR=1.516, 95%CI: 1.086-2.116) in peripheral blood were risk factors for mortality in patients with lung infection. Seven days after admission, the levels of miR-133(OR=1.550, 95%CI: 1.125-2.136), CRP (OR=1.649, 95%CI: 1.213-2.241), and TIM-4(OR=1.609, 95%CI: 1.175-2.202) in peripheral blood were also risk factors for mortality in patients with lung infection. On the day of admission, the levels of miR-133(r1=0.645, P<0.001), CRP (r2=0.726, P<0.001), and TIM-4(r3=0.671, P<0.001) in peripheral blood were positively correlated with the severity of lung infection. The AUC predicted by the combination of indicators three days after admission was 0.941, with a sensitivity of 92.59% and a specificity of 87.86%. The AUC predicted by the combination of indicators seven days after admission was 0.952, with a sensitivity of 88.89% and a specificity of 95.38%. Conclusion The expression levels of miR-133, CRP, and TIM-4 in peripheral blood are positively correlated with the severity of pulmonary infection. The combined prediction of the survival status of patients with pulmonary infection using these three factors has high performance. Patients with high levels of miR-133, CRP, and TIM-4 have a higher risk of mortality in pulmonary infection. Monitoring miR-133, CRP, and TIM-4 can provide guidance for clinical diagnosis and prognosis evaluation.
关键词
肺部感染 /
微小RNA-133 /
C反应蛋白 /
T细胞免疫球蛋白与黏蛋白域4 /
受试者工作特征曲线
Key words
pulmonary infection /
microRNA133 /
C-reactive protein /
T-cell immunoglobulin and mucin domain 4 /
receiver operating characteristic curve
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参考文献
[1] EVANGELOU K, VEROUTIS D, PASCHALAKI K, et al.Pulmonary infection by SARS-CoV-2 induces senescence accompanied by an inflammatory phenotype in severe COVID-19: possible implications for viral mutagenesis[J]. Eur Respir J, 2022, 60(2): 2102951.
[2] MAJOR J, CROTTA S, FINSTERBUSCH K, et al.Endothelial AHR activity prevents lung barrier disruption in viral infection[J]. Nature, 2023, 621(7980): 813-820.
[3] YADAV KK, AWASTHI S.Childhood pneumonia: what's unchanged, and what's new[J]. Indian J Pediatr, 2023, 90(7): 693-699.
[4] 徐欣, 张永明. 血清前白蛋白联合降钙素原、C反应蛋白对颅脑外伤术后并发肺部感染的诊断价值[J]. 中国医药导报, 2024, 21(2): 100-103.
[5] AL-KAFAJI G, AL-MUHTARESH HA, SALEM AH.Expression and clinical significance of miR-1 and miR-133 in pre-diabetes[J]. Biomed Rep, 2021, 14(3): 33.
[6] WANG ZY, CHEN C, SU YZ, et al.Function and characteristics of TIM-4 in immune regulation and disease (Review)[J]. Int J Mol Med, 2023, 51(2): 10.
[7] 张威. 老年社区获得性肺炎严重度指数PSI和CURB-65评分应用价值研究[J]. 临床肺科杂志, 2013, 18(11): 2114-2115.
[8] 葛均波, 徐永健, 王辰. 内科学[M]. 第9版. 北京: 人民卫生出版社, 2018: 41-57.
[9] MA T, TANG Y, WANG TL, et al.Chronic pulmonary bacterial infection facilitates breast cancer lung metastasis by recruiting tumor-promoting MHCIIhi neutrophils[J]. Signal Transduct Target Ther, 2023, 8(1): 296.
[10] 张春梅, 宋杰, 王金祥. 老年COPD伴肺部感染患者外周血细胞形态学变化及其对预后的预测价值[J]. 湖南师范大学学报 (医学版), 2024, 21(2): 51-55.
[11] STOCK CJW, BRAY WG, KOURANOS V, et al.Serum C-reactive protein is associated with earlier mortality across different interstitial lung diseases[J]. Respirology, 2024, 29(3): 228-234.
[12] PLEBANI M.Why C-reactive protein is one of the most requested tests in clinical laboratories[J]. Clin Chem Lab Med, 2023, 61(9): 1540-1545.
[13] KOSKERIDIS F, EVANGELOU E, SAID S, et al.Pleiotropic genetic architecture and novel loci for C-reactive protein levels[J]. Nat Commun, 2022, 13(1): 6939.
[14] FLORIN TA, AMBROGGIO L, BROKAMP C, et al.Biomarkers and disease severity in children with community-acquired pneumonia[J]. Pediatrics, 2020, 145(6): 20193728.
[15] JAGANATH D, REZA TF, WAMBI P, et al.The Role of c-reactive protein as a triage tool for pulmonary tuberculosis in children[J]. J Pediatric Infect Dis Soc, 2022, 11(7): 316-321.
[16] VANDEVANTER DR, HELTSHE SL, SKALLAND M, et al.C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response[J]. J Cyst Fibros, 2022, 21(4): 588-593.
[17] LEVINSON T, WASSERMAN A.C-reactive protein velocity (crpv) as a new biomarker for the early detection of acute infection/inflammation[J]. Int J Mol Sci, 2022, 23(15): 8100.
[18] 杨茜, 高梦琦, 周彤, 等. 血清N端脑钠肽前体、D-二聚体、降钙素原和C反应蛋白水平联合检测对慢性阻塞性肺疾病并发肺部感染患者诊断效能分析[J]. 实用医院临床杂志, 2022, 19(2): 144-147.
[19] TANG D, GE H, TAN ZQ, et al.The factors for the occurrence of pulmonary infection after gastrointestinal surgery and the construction of a predictive model using strem-1 and TIM-4: A retrospective study[J]. Ann Ital Chir, 2024, 95(3): 299-307.
[20] JOSHI S, LÓPEZ L, MOROSI LG, et al. Tim4 enables large peritoneal macrophages to cross-present tumor antigens at early stages of tumorigenesis[J]. Cell Rep, 2024, 43(4): 114096.
[21] CHOW A, SCHAD S, GREEN MD, et al.Tim-4+cavity-resident macrophages impair anti-tumor CD8+T cell immunity[J]. Cancer Cell, 2021, 39(7): 973-988.
[22] 孙源, 赵立涵, 曾玮, 等. 重症肺炎患者血清ANXA1、TIM-4表达水平及临床意义[J]. 临床肺科杂志, 2023, 28(11): 1635-1639.
[23] 禹萌, 任雅芳, 张洪涛, 等. 脑卒中后肺部感染患者血清TIM-4和miR-21含量及其临床意义[J]. 热带医学杂志, 2022, 22(3): 392-395.
[24] PARAYATH NN, GANDHAM SK, AMIJI MM.Tumor-targeted miRNA nanomedicine for overcoming challenges in immunity and therapeutic resistance[J]. Nanomedicine (Lond), 2022, 17(19): 1355-1373.
[25] 孙怀鑫, 邵翔, 徐德宇, 等. 透明细胞肾细胞癌外泌体miR-133a表达及临床意义[J]. 临床肿瘤学杂志, 2023, 28(2): 105-111.
[26] 陈群, 陈希. 血清miR-133a、sCD44v6、胃泌素-17在胃癌和癌前病变筛查中的应用及与Hp-IgG表达的关系[J]. 临床和实验医学杂志, 2024, 23(4): 361-366.
[27] ASAI S, KOMA A, NOHATA N, et al.Impact of miR-1/miR-133 clustered miRNAs: PFN2 facilitates malignant phenotypes in head and neck squamous cell carcinoma[J]. Biomedicines, 2022, 10(3): 663.
[28] 王丛萌, 刘超, 石秋艳. HIF-1α和miR-5787及miR-133在脑梗死肺部感染患者的表达水平及红细胞免疫与炎症反应变化[J]. 热带医学杂志, 2022, 22(5): 656-659+710.
基金
宁夏医科大学科研项目“血清miR-133与肺部感染病情的相关性及临床研究”（XT202000423）
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