| 7 | 0 | 3 |
| 下载次数 | 被引频次 | 阅读次数 |
目的：探讨正五聚蛋白-3(Pentraxin-3,PTX-3)启动子甲基化对复杂性阑尾炎（CA）的早期诊断价值。方法：选取青岛市海慈医疗集团收治的阑尾炎患者及健康体检者作为研究对象，将其分为CA组、单纯性阑尾炎（SA）组及健康体检（HCs）组，观察各组PTX-3血浆浓度、mRNA水平及其启动子甲基化状态，总胆红素（TBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、白蛋白（Alb）、白细胞计数（WBC）、中性粒细胞计数（NEU）、C反应蛋白（CRP）、降钙素原（PCT）等。应用Spearman相关分析检验各变量的相关性。多因素Logistic回归分析进行PTX-3基因甲基化与临床参数的相关性检验。使用ROC曲线分析PTX-3甲基化对CA的诊断价值。结果：血清中PTX-3 mRNA水平及血浆浓度在CA组表达明显高于SA组和HCs组，而其PTX-3甲基化频率显著低于SA组及HCs组（P<0.05）。PTX-3基因的甲基化状态与炎症指标（WBC、NEU、PCT、CRP）明显相关（P<0.05）。多元Logistic回归分析表明，WBC、CRP及PCT是PTX-3基因启动子甲基化的独立影响因素（P<0.05）。Spearman相关分析表明，CA组外周血PTX-3 mRNA水平与其甲基化状态呈负相关（P<0.001）;PTX-3 mRNA水平与WBC、NEU、CRP及PCT水平呈正相关（P<0.05）。PTX-3基因甲基化诊断CA的敏感度为94.67%，特异度为76.67%。当从SA患者中诊断CA时，PTX-3甲基化的AUC明显高于WBC、NEU、CRP和PCT(P<0.001)。结论：PTX-3启动子甲基化调控PTX-3的表达，参与急性阑尾炎的发病过程。可用于监测CA患者的炎症状态，作为一种早期诊断的非侵入性生物学标志。
Abstract：Objective: To investigate the early diagnosis value of Pentraxin-3(PTX-3) promoter methylation for complicated appendicitis. Methods: Patients with appendicitis and healthy physical examination from Qingdao Hiser Medical Group were selected as the research objects, and they were divided into complicated appendicitis group(CA),simple appendicitis group(SA) and healthy control group(HCs). Plasma PTX-3 levels, mRNA expression, promoter methylation status, and clinical parameters—including total bilirubin(TBIL), alanine aminotransferase(ALT), aspartate aminotransferase(AST), albumin(Alb), white blood cell count(WBC), neutrophil count(NEU), C-reactive protein(CRP),and procalcitonin(PCT)—were analyzed.in each group. Spearman correlation analysis was used to test the correlation of variables. Multivariate Logistic regression analysis was used to test the correlation between PTX-3 gene methylation and clinical parameters. The area under the receiver operating characteristic curve(AUC) was used to analyze the diagnostic value of PTX-3 methylation for CA. Results: The mRNA level and plasma concentration of PTX-3 in CA group were significantly higher than those in SA group and HCs group, while the methylation frequency of PTX-3 in CA group was significantly lower than that in SA group and HCs group(P<0.05). The methylation status of PTX-3 gene was significantly correlated with inflammatory markers(WBC, NEU, PCT, CRP)(P<0.05). Multivariate Logistic regression analysis showed that WBC, CRP and PCT were independent influencing factors of PTX-3 gene promoter methylation(P<0.05). Spearman correlation analysis showed that the PTX-3 mRNA level in peripheral blood of CA patients was negatively correlated with its methylation status(P<0.001). PTX-3 mRNA level was positively correlated with WBC, NEU, CRP and PCT levels(P<0.05). The sensitivity and specificity of PTX-3 gene methylation in the diagnosis of CA were 94.67% and 76.67%, respectively. When CA was diagnosed from SA patients, the AUCs of PTX-3 methylation were significantly higher than those of WBC, NEU, CRP and PCT(P<0.001). Conclusion: PTX-3 promoter methylation is involved in the pathogenesis of AA by regulating the expression of PTX-3. It can be used to monitor the inflammatory state of patients with complicated appendicitis and serve as a non-invasive early diagnosis biomarker for complicated appendicitis.
[1] Stewart B, Khanduri P, McCord C, et al. Global disease burden of conditions requiring emergency surgery[J]. Br J Surg, 2014, 101(1):9-22. DOI:10.1002/bjs.9376.
[2] Del PC, Munoz R, Rada G. Laparoscopic versus open appendectomy for complicated appendicitis[J]. Medwave, 2018, 18(8):7370. DOI:10.5867/medwave.2018.08.7369.
[3] Vilahur G, Badimon L. Biological actions of pentraxins[J]. Vascul Pharmacol, 2015, 73:38-44. DOI:10.1016/j.vph.2015.05.001.
[4] Zhang J, Koussih L, Shan L, et al. TNF up-regulates Pentraxin3 expression in human airway smooth muscle cells via JNK and ERK1/2MAPK pathways[J]. Allergy Asthma Clin Immunol, 2015, 11:37.DOI:10.1186/s13223-015-0104-y.
[5] Siljan WW, Holter JC, Michelsen AE, et al. Inflammatory biomarkers are associated with aetiology and predict outcomes in communityacquired pneumonia:results of a 5-year follow-up cohort study[J].ERJ Open Res, 2019, 5(1):00014-2019. DOI:10.1183/23120541.00014-2019.
[6] Kim HS, Won S, Lee EK, et al. Pentraxin 3 as a clinical marker in children with lower respiratory tract infection[J]. Pediatr Pulmonol,2016, 51(1):42-48. DOI:10.1002/ppul.23199.
[7] Yu J,Ni M, Xu J, et al. Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis[J]. BMC Cancer, 2002, 2:29. DOI:10.1186/1471-2407-2-29.
[8] Bonavita E, Gentile S, Rubino M, et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer[J].Cell, 2015, 160(4):700-714. DOI:10.1016/j.cell.2015.01.004.
[9] Ates U, Bahadir K, Ergun E, et al. Determination of pentraxin 3 levels in diagnosis of appendicitis in children[J]. Pediatr Int, 2020, 62(5):624-628. DOI:10.1111/ped.14131.
[10] Folwaczny M, Karnesi E, Berger T, et al. Clinical association between chronic periodontitis and the leukocyte extravasation inhibitors developmental endothelial locus-1 and pentraxin-3[J]. Eur J Oral Sci, 2017, 125(4):258-264. DOI:10.1111/eos.12357.
[11] Guo TM, Huang LL, Liu K, et al. Pentraxin 3(PTX3)promoter methylation associated with PTX3 plasma levels and neutrophil to lymphocyte ratio in coronary artery disease[J]. J Geriatr Cardiol, 2016,13(8):712-717. DOI:10.11909/j.issn.1671-5411.2016.08.010.
[12] Yu CW, Juan LI, Wu MH, et al. Systematic review and metaanalysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis[J].Br J Surg, 2013, 100(3):322-329. DOI:10.1002/bjs.9008.
[13] Giacomini A, Ghedini GC, Presta M, et al. Long pentraxin 3:A novel multifaceted player in cancer[J]. Biochim Biophys Acta Rev Cancer, 2018, 1869(1):53-63. DOI:10.1016/j.bbcan.2017.11.004.
[14] Razvina O, Jiang S, Matsubara K, et al. Differential expression of pentraxin 3 in neutrophils[J]. Exp Mol Pathol, 2015, 98(1):33-40.DOI:10.1016/j.yexmp.2014.11.009.
[15] Aygun A, Katipoglu B, Imamoglu M, et al. Diagnostic Value of Plasma Pentraxin-3 in Acute Appendicitis[J]. J Invest Surg, 2019,32(2):143-148. DOI:10.1080/08941939.2017.1381789.
[16] Oztan MO, Aksoy GA, Ozdemir T, et al. Pentraxin-3:A strong novel biochemical marker for appendicitis in children[J]. Am J Emerg Med, 2019, 37(10):1912-1916. DOI:10.1016/j.ajem.2019.01.010.
[17] Heyn H and Esteller M. DNA methylation profiling in the clinic:applications and challenges[J]. Nat Rev Genet, 2012, 13(10):679-92. DOI:10.1038/nrg3270.
[18] Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation[J]. N Engl J Med, 2003, 349(21):2042-54. DOI:10.1056/NEJMra023075.
[19] Wang JX, He YL, Zhu ST, et al. Aberrant methylation of the 3q25tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma[J]. World J Gastroenterol, 2011, 17(37):4225-30. DOI:10.1056/NEJMra023075.
[20] Meryk P, Dumnicka P, Kusnierz CB, et al. Diagnostic importance of pentraxins at the early phase of acute pancreatitis[J]. Przegl Lek,2014, 71(6):309-313.
[21]朱虹，曹丹，朱大龙.pentraxin 3蛋白与糖尿病肾病相关研究进展[J].中华糖尿病杂志，2018,10(4):299-301. DOI:10.3760/cma.j.issn.1674-5809.2018.04.013.
[22] Hansen MB, Rasmussen LS, Garred P, et al. Pentraxin-3 as a marker of disease severity and risk of death in patients with necrotizing soft tissue infections:a nationwide, prospective, observational study[J]. Crit Care, 2016, 20:4. DOI:10.1186/s13054-016-1210-z.
[23] Hu C, Zhou Y,Liu C, et al. Pentraxin-3, procalcitonin and lactate as prognostic markers in patients with sepsis and septic shock[J]. Oncotarget, 2018, 9(4):5125-5136. DOI:10.18632/oncotarget.23701.
[24] Hamed S, Behnes M, Pauly D, et al. Diagnostic value of Pentraxin-3in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions[J]. BMC Infect Dis, 2017, 17(1):554. DOI:10.1186/s12879-017-2606-3.
[25]马天翼，张骞，赵宏伟，等.复杂性阑尾炎发病风险因素分析[J].中国现代普通外科进展，2023,26(3):239-241. DOI:10.3969/j.issn.1009-9905.2023.03.018.
[26]张新丽，李凯江，赵蒲宇，等.未成熟粒细胞百分比在预测儿童急性阑尾炎严重程度中的临床价值[J].中国现代普通外科进展，2024,27(7):533-537. DOI:10.3969/j.issn.1009-9905.2024.07.006.
[27] Gül VO, Destek S. Using pentraxin-3 for diagnosing acute appendicitis and predicting perforation:A prospective comparative methodological study[J]. Ulus Travma Acil Cerrahi Derg, 2020, 26(1):21-29. DOI:10.14744/tjtes.2019.27916.
[28] Perez-Novo C A, Bachert C. DNA methylation, bacteria and airway inflammation:latest insights[J]. Curr Opin Allergy Clin Immunol,2015, 15(1):27-32. DOI:10.1097/ACI.0000000000000130.
基本信息:
DOI：
中图分类号:R656.8
引用信息:
[1]孙风波,邢智远,马红等.Pentraxin-3启动子甲基化对复杂性阑尾炎的早期诊断价值[J].中国现代普通外科进展,2025,28(05):343-349.
基金信息:
青岛市医药卫生科研计划项目(2021-WJZD065)