高迁移率族蛋白A2在老年特发性肺纤维化病人血清中的表达及其与肺纤维化程度和预后的关系

doi:10.3969/j.issn.1003-9198.2022.02.007

摘要/Abstract

摘要： 目的探讨高迁移率族蛋白A2(HMGA2)在老年特发性肺纤维化(IPF)病人血清中的表达及其与肺纤维化程度和预后的关系。方法选取2017～2018年期间在我院进行治疗的老年IPF病人102例,所有病人均进行为期2年的随访,根据预后情况将病人分为预后良好组以及预后不良组。收集所有病人的临床资料,检测血清HMGA2以及Ⅳ型胶原(Ⅳ C)、透明质酸(HA)的水平。采用Pearson法分析血清HMGA2和纤维化指标的相关性。采用多因素非条件Logistic回归模型分析IPF病人预后不良的影响因素。采用ROC曲线分析血清HMGA2对IPF病人预后的评估价值。结果 102例IPF病人中48例预后不良,54例预后良好。预后不良组的吸烟比例及Ⅳ C、HA、血清HMGA2水平均显著高于预后良好组,第1秒用力呼气容积占预计值百分比(FEV1%)、一氧化碳弥散量占预计值百分比(DLCO%)均显著低于预后良好组(P<0.01)。Pearson相关性分析显示,IPF病人血清HMGA2水平与Ⅳ C、HA水平均呈正相关(P<0.01)。多因素分析显示,Ⅳ C、HA、HMGA2是IPF病人预后不良的危险因素(P<0.05),DLCO%则是保护因素(P<0.05)。血清HMGA2预测IPF的病人预后不良的ROC曲线下面积为0.815(95%CI:0.733～0.897)。结论 HMGA2在老年IPF病人血清中的表达水平与肺纤维化程度和预后密切相关,HMGA2可能通过调控肺纤维化进展参与疾病的发生、发展。

关键词: 特发性肺纤维化, 老年人, 高迁移率族蛋白A2, 预后

Abstract: Objective To investigate the expression of high mobility group protein A2 (HMGA2) in the serum of elderly patients with idiopathic pulmonary fibrosis (IPF), and to investigate the relationship with the prognosis. Methods A total of 102 elderly patients with IPF who were treated in our hospital from 2017 to 2018 were selected. All patients were followed up for 2 years. The patients were divided into the good prognosis group and the poor prognosis group according to the prognosis. The clinical data of all patients were collected, and the serum levels of HMGA2, type Ⅳ collagen (Ⅳ C) and hyaluronic acid (HA) were detected. Pearson correlation analysis was used to analyze the correlation between serum HMGA2 and fibrosis indexes. Multivariate unconditional Logistic regression model was used to analyze the influencing factors of poor prognosis in the IPF patients. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of serum HMGA2 in the patients with IPF. Results The follow-up results showed that 48 out of the 102 IPF patients presented with poor prognosis, and 54 showed good prognosis. The proportion of smoking, the serum levels of Ⅳ C, HA and HMGA2 in the poor prognosis group were significantly higher, and the levels of FEV1% and DLCO% were significantly lower than those in the good prognosis group (P<0.01). Pearson correlation analysis showed that the serum level of HMGA2 was positively correlated with the serum level of Ⅳ C and HA (P<0.01). Multivariate analysis showed that Ⅳ C, HA, and HMGA2 were risk factors for poor prognosis in the IPF patients (P<0.05), and DLCO% was a protective factor (P<0.05). The area under the ROC curve of serum HMGA2 predicting poor prognosis of the IPF patients was 0.815 (95% CI: 0.733-0.897). Conclusions The serum level of HMGA2 in the IPF patients is closely related to the prognosis. HMGA2 may participate in the occurrence and development of the disease by regulating the progression of pulmonary fibrosis.

Key words: idiopathic pulmonary fibrosis, aged, high mobility group protein A2, prognosis

中图分类号:

R 563

岳圆圆, 张玉扬, 韩慧, 李忠梅. 高迁移率族蛋白A2在老年特发性肺纤维化病人血清中的表达及其与肺纤维化程度和预后的关系[J]. 实用老年医学, 2022, 36(2): 134-137.

YUE Yuan-yuan, ZHANG Yu-yang, HAN Hui, LI Zhong-mei. Expression of high mobility group protein A2 in the serum of elderly patients with idiopathic pulmonary fibrosis and its relationship with the prognosis[J]. Practical Geriatrics, 2022, 36(2): 134-137.

参考文献

[1] LEDERER D J,MARTINEZ F J.Idiopathic pulmonary fibrosis[J].N Engl J Med,2018,378(19):1811-1823.
[2] SGALLA G,IOVENE B,CALVELLO M,et al.Idiopathic pulmonary fibrosis: pathogenesis and management[J].Respir Res,2018,19(1):32.
[3] 李怡华,叶俏.特发性肺纤维化治疗药物临床试验进展[J].中华结核和呼吸杂志,2020,43(3):256-262.
[4] WANG Y,LE Y,XUE J Y,et al.Let-7d miRNA prevents TGF-β1-induced EMT and renal fibrogenesis through regulation of HMGA2 expression[J].Biochem Biophys Res Commun,2016,479(4):676-682.
[5] XIAO Y,LIU R,LI X,et al.Long noncoding RNA H19 contributes to cholangiocyte proliferation and cholestatic liver fibrosis in biliary atresia[J].Hepatology,2019,70(5):1658-1673.
[6] YU X H, ZHAI R N, HUA B Y,et al.miR-let-7d attenuates EMT by targeting HMGA2 in silica-induced pulmonary fibrosis[J]. RSC Advances, 2019,9(34):19355-19364.
[7] 中华医学会呼吸病学分会间质性肺疾病学组.特发性肺纤维化诊断和治疗中国专家共识[J].中华结核和呼吸杂志,2016,39(6):427-432.
[8] 雷凯春,岳红梅,周婷婷.特发性肺纤维化治疗新进展[J].中国呼吸与危重监护杂志,2019,18(2):97-101.
[9] XIONG Y,ZHANG J,SHI L,et al.NOGO-B promotes EMT in lung fibrosis via MMP14 mediates free TGF-beta1 formation[J].Oncotarget,2017,8(41):71024-71037.
[10] SAKUMA Y.Epithelial-to-mesenchymal transition and its role in EGFR-mutant lung adenocarcinoma and idiopathic pulmonary fibrosis[J].Pathol Int,2017,67(8):379-388.
[11] 夏婷婷,张丽婷,陈芳,等.特发性肺纤维化的细胞学研究进展[J].医学研究生学报,2016,29(3):314-318.
[12] 梁春联,权晓娟,章琳,等.特发性肺纤维化患者血清KL-6、CCL18和microRNA-21的表达及意义[J].中国临床研究,2020,33(4):452-455.
[13] WEI P, XIE Y, ABEL P W,et al.Transforming growth factor (TGF)-β1-induced miR-133a inhibits myofibroblast differentiation and pulmonary fibrosis[J].Cell Death Dis,2019,10(9):670.
[14] MAK K M,MEI R.Basement membrane type Ⅳ collagen and laminin: An overview of their biology and value as fibrosis biomarkers of liver disease[J].Anat Rec (Hoboken),2017,300(8):1371-1390.
[15] NEUMAN M G,COHEN L B,NANAU R M.Hyaluronic acid as a non-invasive biomarker of liver fibrosis[J].Clin Biochem,2016,49(3):302-315.
[16] 苏奕亮,翁东,周瑛,等.血清LN、Ⅳ C、P Ⅲ NP、HA与特发性肺纤维化严重度和预后的相关性[J].中华急诊医学杂志,2018,27(2):188-193.
[17] WANG Y C,LIU J S,TANG H K,et al.miR221 targets HMGA2 to inhibit bleomycin induced pulmonary fibrosis by regulating TGFβ1/Smad3-induced EMT[J].Int J Mol Med,2016,38(4):1208-1216.
[18] 李鹏,刘咏梅,刘振华.敲减HMGA2基因抑制TGF-β1诱导的人胚肺成纤维细胞生长及胶原合成[J].中国病理生理杂志,2019,35(9):1648-1653.
[19] XIONG L,TANG Y,TANG J,et al.Downregulation of lncRNA HOTTIP suppresses the proliferation, migration, and invasion of oral tongue squamous cell carcinoma by regulation of HMGA2-mediated Wnt/β-catenin pathway[J].Cancer Biother Radiopharm,2020,35(9):720-730.