S100-A8蛋白在脊柱结核患者外周血中的表达及临床意义

Expression and clinical significance of S100-A8 protein in peripheral blood of patients with spinal tuberculosis

中文关键词:  脊柱结核  蛋白质组学  S100-A8  生物标志物

英文关键词:Spinal tuberculosis  Proteomics  S100-A8  Biomarkers

中文摘要:

  【摘要】 目的：分析S100-A8蛋白在脊柱结核患者外周血中的表达与临床诊断的相关性，评价其作为脊柱结核诊断标志物的价值。方法：收集2018年9月～2021年6月宁夏医科大学总医院脊柱骨科收治的脊柱结核患者100例作为观察组，健康体检者30例作为对照组。观察组男性50例，女性50例，年龄49.5±16.3岁；对照组男性12例，女性18例，年龄53.4±9.7岁。两组各选取3例样本进行蛋白质组学检测并筛选差异蛋白，结合脊柱结核信号通路，确认目标蛋白。选取50例观察组与30例对照组，运用酶联免疫吸附测定法（enzyme-linked immunosorbent assay，ELISA）测定并比较两组血清目标蛋白表达水平。收集观察组临床病历资料，包括：年龄、性别、病程、实验室检查、细菌培养、T-SPOT、抗酸染色、病理学及影像学资料，收集对照组实验室检查并与观察组进行比较；采用T-test分析目标蛋白在观察组各项临床资料之中的表达差异；通过线性回归及双变量斯皮尔曼相关性分析目标蛋白与观察组临床资料的相关性；受试者工作特征曲线 （receiver operating characteristic，ROC）曲线分析目标蛋白联合STB常用诊断指标的价值。结果：S100-A8蛋白具有诊断脊柱结核的价值（AUC=0.931，P<0.001），在观察组外周血中表达水平（59.04±19.37ng/ml）显著高于对照组（43.16±10.07ng/ml）（P<0.05）。观察组CRP及ESR显著高于对照组（P<0.05），两组间白细胞、中性粒细胞、淋巴细胞无统计学差异（P＞0.05）。观察组中、细菌学培养阳性16例，阴性84例；T-SPOT阳性80例，阴性20例；抗酸染色阳性19例，阴性81例；病理学阳性73例，阴性27例；影像学诊断阳性76例，阴性24例。S100-A8蛋白在观察组的临床分组（年龄、性别、病程、白细胞、淋巴细胞、中性粒细胞）无统计学意义（P>0.05），在影像学诊断中差异显著（P<0.05），在ESR、CRP、T-SPOT、病理学结果、抗酸染色结果、细菌学检测中差异极显著（P<0.01）。线性回归分析表明S100-A8蛋白表达水平与CRP及ESR均表现为显著正相关（R2分别为0.166和0.266，P<0.01）。双变量斯皮尔曼相关性分析显示其与CRP及ESR均表现为显著正相关（R2分别为0.621和0.681，P<0.01），而与白细胞、病程、中性粒细胞及淋巴细胞相对值的变化无相关性（P>0.05）。ROC曲线分析显示其联合细菌学检测、T-SPOT结果、影像学诊断、抗酸染色结果、病理学具有诊断价值（AUC＞0.6，P<0.05）。结论：S100-A8蛋白在脊柱结核患者与健康人外周血中存在表达差异，可能成为诊断脊柱结核的新型候选生物标志物。

英文摘要:

  【Abstract】 Objectives: To analyze the correlation between the expression of S100-A8 protein in the peripheral blood of patients with spinal tuberculosis(STB) and its clinical diagnosis, and to evaluate its value as a diagnostic marker for spinal tuberculosis. Methods: 100 patients with STB who were admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were included as the observation group and 30 healthy people were enrolled as the control group. The observation group included 50 males and 50 females, with an average of 49.5±16.3 years; the control group consisted of 12 males and 18 females, with an average age of 53.4±9.7 years. Three samples from each group were selected for proteomic detection and differential proteins were screened, and target protein was confirmed after considering spinal tuberculosis signal pathway. 50 cases of observation group and 30 cases of control group were selected, Enzyme-linked immunosorbent assay(ELISA) was used to measure and compare the expressions of target proteins in the two groups. The clinical data were collected, including age, gender, course of disease, laboratory examination, bacterial culture, T-SPOT, acid-fast stain(AFS), pathology, and imaging data, and the laboratory test data of the observation group were also collected and compared with the control group. The expression difference of target protein in various clinical data of STB patients was analyzed; the correlation between target protein and clinical data of STB patients was analyzed by linear regression and Spearman correlation; ROC curve analysis was used to analyze the value of target protein combining traditional STB diagnostic indicators. Results: S100-A8 protein had the value in the diagnosis of STB was (AUC=0.931, P<0.001), and the expression of S100-A8 protein in peripheral blood of patients of observation group(59.04±19.37ng/ml) was significantly higher than that of the control group(43.16±10.07ng/ml)(P<0.05). The measurement results of C-reactive protein(CRP) and ESR in the peripheral blood of spinal tuberculosis patients were also significantly higher than those of the control group(P＜0.05). There was no significant difference in WBC, NEUT% and LYM% between the two groups(P＞0.05). In the observation group, there were 16 cases of positive bacteriological culture and 84 cases of negative culture; 80 cases of T-SPOT positive patients and 20 negative patients; 19 AFS positive patients and 81 negative patients; 73 pathological positive patients and 27 negative patients; 76 patients with positive imaging diagnosis and 24 patients with negative diagnosis. There was no significant difference in the S100-A8 protein in the clinical grouping (age, gender, course of disease, white blood cell value, lymphocyte value, and neutrophil value) of the observation group(P>0.05), but there was a significant difference in imaging diagnosis(P<0.05), and in terms of ESR, CRP, T-SPOT, pathological results, AFS results, bacteriological detection, the differences were extremely significant(P<0.01). Linear regression analysis showed that S100-A8 protein expression level was significantly positively correlated with CRP and ESR(R2 were 0.166 and 0.266, P<0.01). Bivariate Spearman correlation analysis showed that it was significantly positively correlated with CRP and ESR(R2 were 0.621 and 0.681, P<0.01), while there was no correlation with the changes in the relative values of white blood cells, disease course, neutrophils and lymphocytes. ROC curve analysis showed its combining with bacteriological detection, T-SPOT results, diagnostic imaging, AFS results, and pathological results were with diagnostic values(AUC>0.6, P<0.05). Conclusions: S100-A8 protein has different expressions in peripheral blood of STB patients and healthy people, which is expected to become a new candidate biomarker for the diagnosis of STB.