[1]刘思哲,安万花,郭淑利,等.锌指蛋白382在弥漫大B细胞淋巴瘤组织中的表达及临床意义[J].新乡医学院学报,2024,(1):037-42.[doi:10.7683/xxyxyxb.2024.01.007]
　LIU Sizhe,AN Wanhua,GUO Shuli,et al.Expression and clinical significance of zinc finger protein 382 in diffuse large B-cell lymphoma[J].Journal of Xinxiang Medical University,2024,(1):037-42.[doi:10.7683/xxyxyxb.2024.01.007]
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锌指蛋白382在弥漫大B细胞淋巴瘤组织中的表达及临床意义
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
期数:
2024年1
页码:
037-42
栏目:
临床研究
出版日期:
2024-01-05

文章信息/Info

Title:
Expression and clinical significance of zinc finger protein 382 in diffuse large B-cell lymphoma
作者:
刘思哲1; 2; 安万花2; 郭淑利2; 王慧睿2; 肖蓬莉2; 王万里2; 王双琳1; 2
（1.新乡医学院，河南　新乡　453003；2.洛阳市中心医院血液科，河南　洛阳　471009）
Author(s):
LIU Sizhe1; 2; AN Wanhua2; GUO Shuli2; WANG Huirui2; XIAO Pengli2; WANG Wanli2; WANG Shuanglin1; 2
（1.Xinxiang Medical University,Xinxiang 453003,Henan Province,China;2.Department of Hematology,Luoyang Central Hospital,Luoyang 471009,Henan Province,China）
关键词:
弥漫大B细胞淋巴瘤; 锌指蛋白382; 临床病理特征; 预后
Keywords:
diffuse large B-cell lymphoma; zinc finger protein 382; clinicopathological features; prognosis
分类号:
R733.1
DOI:
10.7683/xxyxyxb.2024.01.007
文献标志码:
A
摘要:
目的　探讨锌指蛋白382(ZNF382)在弥漫大B细胞淋巴瘤(DLBCL)组织中的表达及其与DLBCL患者临床病理特征和预后的关系。
方法　选择2014年1月至2018年12月洛阳市中心医院血液科收治的57例DLBCL患者为研究对象。收集患者的活检病理标本及临床资料；另取洛阳市中心医院病理科保存的20例反应性增生淋巴结组织作为对照组。采用En vision二步法检测DLBCL 组织和反应性增生淋巴组织中ZNF382表达，比较DLBCL 组织和反应性增生淋巴组织中ZNF382表达差异。采用单因素分析ZNF382表达与DLBCL患者年龄、性别、肿瘤原发部位、Ann Arbor分期、国际预后指数(IPI)评分、Hans分型、B症状、骨髓浸润、巨大包块、美国东部肿瘤协作组(ECOG)评分、β2微球蛋白（β2-MG）、血清乳酸脱氢酶(LDH)、Ki67、化学治疗方案等临床资料的关系；采用Kaplan-Meier法绘制生存曲线，应用log-rank检验和Cox比例风险回归模型进行单因素和多因素生存分析。
结果　DLBCL组织中ZNF382表达水平显著低于反应性增生淋巴结组织 (Z=-5.056，P<0.01)。ZNF382表达水平与DLBCL患者的IPI评分、Ann Arbor分期、Hans分型、B症状、骨髓浸润、巨大包块相关(P<0.05)；ZNF382表达水平与DLBCL患者的性别、年龄、原发部位、ECOG评分、β2-MG、血清LDH、Ki67、化学治疗方案是否联合利妥昔单抗无关（P>0.05）。57例DLBCL患者中治疗有效者36例（63.20%），无效者21例（36.80%）；治疗有效患者肿瘤组织中ZNF382表达水平显著高于治疗无效患者（Z=-2.895，P<0.05）。ZNF382高表达组DLBCL患者2 a 无事件生存率显著高于ZNF382低表达组（χ2=17.955，P<0.001)。单因素生存分析结果显示，女性、淋巴结内原发、有B症状、有骨髓浸润、有巨大包块、IPI评分≥3分、β2-MG升高、Ki67>70%、非生发中心B细胞样淋巴癌、Ann Arbor分期Ⅲ~Ⅳ期、ZNF382低表达是DLBCL患者预后不良的危险因素（P<0.05）；多因素分析结果表明，淋巴结内原发、Ann Arbor分期Ⅲ~Ⅳ期、ZNF382低表达是DLBCL患者预后不良的独立影响因素（P<0.05）。
结论　ZNF382蛋白在DLBCL组织中呈低表达，与DLBCL的发生、发展及预后密切相关，可作为评估DLBCL预后的指标。
Abstract:
Objective　To investigate the expression of zinc finger protein 382 (ZNF382) in diffuse large B-cell lymphoma (DLBCL) tissue and its relationship with clinical pathological characteristics and prognosis of DLBCL patients.
Methods　A total of 57 DLBCL patients admitted to the Department of Hematology,Luoyang Central Hospital from January 2014 to December 2018 were selected as the research subjects.The biopsy pathological specimens and clinical data of DLBCL patients were collected;another 20 patients of reactive proliferative lymph node tissue preserved in the Department of Pathology,Luoyang Central Hospital were taken as the control group.The expression of ZNF382 in DLBCL tissue and reactive proliferative lymph node tissue was detected by En vision two-step method.The difference of ZNF382 expression was compared between DLBCL tissue and reactive proliferative lymph node tissue.The correlations of ZNF382 expression with the clinical features such as age,gender,primary tumor site,Ann Arbor stage,international prognostic index(IPI) score,Hans typing,B-symptoms,bone marrow infiltration,giant masses,Eastern Cooperative Oncology Group (ECOG) score,β2-microglobulin(β2-MG),serum lactate dehydrogenase (LDH),Ki67,and chemotherapy regimen of DLBCL patients were analyzed by univariate analysis;the survival curve was drawed by Kaplan Meier method,and the univariate and multivariate survival analysis were performed by log-rank tests and Cox proportional risk regression models.
Results　The expression level of ZNF382 in DLBCL tissue was significantly lower than that in reactive proliferative lymph node tissue (Z=-5.056,P<0.01).The expression level of ZNF382 was correlated with IPI score,Ann Arbor stage,Hans typing,B-symptoms,bone marrow infiltration and giant masses of DLBCL patients (P<0.05);the expression level of ZNF382 was not associated to gender,age,primary site,ECOG score,β2-MG,serum LDH,Ki67,and whether the chemotherapy regimen combined with rituximab or not of DLBCL patients(P>0.05).Among the 57 DLBCL patients,the treatment was effective in 36 patients (63.20%) and ineffective in 21 patients (36.80%);the expression level of ZNF382 in tumor tissue of DLBCL patients with effective treatment was significantly higher than that of DLBCL patients with ineffective treatment (Z=-2.895,P<0.05).The 2-year event free survival rate of DLBCL patients in the ZNF382 high expression group was significantly higher than that in the ZNF382 low expression group（χ2=17.955,P<0.001).The results of univariate survival analysis showed that female,primary lymph nodes,B-symptoms,bone marrow infiltration,giant masses,IPI score≥3,elevated β2-MG,Ki67>70%,non-germinal center B-cell-like lymphoma,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were risk factors for poor prognosis in DLBCL patients (P<0.05).The results of multivariate analysis showed that primary lymph nodes,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were independent influencing factors for poor prognosis in DLBCL patients (P<0.05).
Conclusion　ZNF382 protein is low expressed in the tumor tissues of DLBCL patients,which is closely related to the occurrence,development and prognosis of DLBCL;and it can be used as an indicator for evaluating the prognosis of DLBCL.

参考文献/References:

［1］　FAROOQ U,MAURER M J,THOMPSON C A,et al.Clinical hetero-geneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy［J］. Br J Haematol,2017,179(1):50-60.
［2］　TAKAHARA T,NAKAMURA S,TSUZUKI T,et al.The immunology of DLBCL［J］.Cancers (Basel),2023,15(3):835.
［3］　CABANILLAS F,SHAH B.Advances in diagnosis and management of diffuse large B-cell lymphoma［J］. Clin Lymphoma Myeloma Leuk,2017,17(12):783-796.
［4］　HONG J,KIM S J,CHANG M H,et al.Improved prognostic stratification using NCCN- and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma［J］. Oncotarget,2017,8(54):92171-92182.
［5］　MARTELLI M,FERRERI A J,AGOSTINELLI C,et al.Diffuse large B-cell lymphoma［J］.Crit Rev Oncol Hematol,2013,87(2):146-171.
［6］　BIGGAR K K,STOREY K B.Functional impact of microRNA regulation in models of extreme stress adaptation［J］.J Mol Cell Biol,2018,10(2):93-101.
［7］　LI S,HE X,WANG Y,et al.Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer［J］.Genes Dis,2022,10(2):568-582.
［8］　GERLACH M M,JUSKEVICIUS D,VELA V,et al.Bone marrow infiltration of angioimmunoblastic T-cell lymphoma:identification and prognostic impact of histologic patterns and diagnostic application of ancillary phenotypic and molecular analyses［J］.Arch Pathol Lab Med,2020,144(5):602-611.
［9］　中华医学会血液学分会,中国抗癌协会淋巴瘤专业委员会.中国弥漫大B细胞淋巴瘤诊断与治疗指南(2013年版)［J］.中华血液学杂志,2013,34(9):816-819.
CHINESE SOCIETY OF HEMATOLOGY,CHINESE MEDICAL ASSOCIATION/CHINESE SOCIETY OF LYMPHOMA,CHINESE ANTI-CANCER ASSOCIATION.Chinese guidelines for diagnosis and treatment of difuse large B cell lymphoma (2013)［J］.Chin J Hematol,2013,34(9):816-819.
［10］　WANG X,WANG J,JIA Y,et al.Methylation decreases the Bin1 tumor suppressor in ESCC and restoration by decitabine inhibits the epithelial mesenchymal transition［J］.Oncotarget,2017,8(12):19661-19673.
［11］　贺白,朱丹霞,晁红颖.miR-181b在弥漫大B细胞淋巴瘤中表达及功能研究［J］.中国实验血液学杂志,2018,26(4):1111-1115.
HE B,ZHU D X,CHAO H Y.Expression and function of miR-181b in diffuse large B cell lymphoma［J］.J Exper Hematol,2018,26(4):1111-1115.
［12］　TILL B G.Maintenance therapy in diffuse large B cell lymphoma and mantle cell lymphoma［J］.Curr Treat Options Oncol,2018,19(9):45.
［13］　朱逸东,甘欣锦.扶正解毒方辨治弥漫大B细胞淋巴瘤免疫逃逸的临床研究［J］.中医学报,2022,37(2):408-412.
ZHU Y D,GAN X J.Clinical study on Fuzheng Jiedu Recipe in treating diffuse large B-cell lymphoma immune escape［J］.Acta Chin Med,2022,37(2):408-412.
［14］　WANG J,ZHANG Y,LIU X,et al.Annexin A5 inhibits diffuse large B-cell lymphoma cell invasion and chemoresistance through phosphatidylinositol 3-kinase signaling［J］.Oncol Rep,2014,32(6):2557-2563.
［15］　SOBOCI N＇SKA J,MOLENDA S,MACHNIK M,et al.KRAB-ZFP transcriptional regulators acting as oncogenes and tumor suppre-ssors:an overview［J］.Int J Mol Sci,2021,22(4):2212.
［16］　WANG W,CAI J,LIN Y,et al.Zinc fingers function cooperatively with KRAB domain for nuclear localization of KRAB-containing zinc finger proteins［J］.PLoS One,2014,9(3):e92155.
［17］　STOLL G A,PANDILOSKI N,DOUSE C H,et al.Structure and functional mapping of the KRAB-KAP1 repressor complex［J］.EMBO J,2022,41(24):e111179.
［18］　JEN J,WANG Y C.Zinc finger proteins in cancer progression［J］.J Biomed Sci,2016,23(1):53.
［19］　CHEN S,XIAO Z,ZHOU J,et al.ZNF382:a transcription inhibitor down-regulated in multiple tumors due to promoter methylation［J］.Clin Chim Acta,2020,500:220-225.
［20］　DANG S,ZHOU J,CHEN Y,et al.Dynamic expression of ZNF382 and its tumor-suppressor role in hepatitis B virus-related hepatocellular carcinogenesis［J］.Oncogene,2019,38(24):4804-4819.
［21］　王进龙,王建,田春艳.KRAB型锌指蛋白的进化及在物种演化中的功能［J］.遗传,2016,38(11):971-979.
WANG J L,WANG J,TIAN C Y.Evolution of KRAB-containing zinc finger proteins and their roles in species evolution［J］.Hereditas(Beijing),2016,38(11):971-978.
［22］　ZHANG C,XIANG T,LI S,et al.The novel 19q13 KRAB zinc-finger tumour suppressor ZNF382 is frequently methylated in oesophageal squamous cell carcinoma and antagonises Wnt/β-catenin signalling［J］.Cell Death Dis,2018,9(5):573.
［23］　PEI L,HE X,LI S,et al.KRAB zinc-finger protein 382 regulates epithelial-mesenchymal transition and functions as a tumor suppressor,but is silenced by CpG methylation in gastric cancer［J］.Int J Oncol,2018,53(3):961-972.
［24］　MA K,CAO B,GUO M.The detective,prognostic,and predictive value of DNA methylation in human esophageal squamous cell carcinoma［J］.Clin Epigenet,2016,8(1):43.
［25］　LIU Z,CHENG X,ZHANG L,et al.A panel of DNA methylated markers predicts metastasis of pN0M0 gastric carcinoma:a prospective cohort study［J］.Br J Cancer,2019,121(7):529-536.

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更新日期/Last Update: 2024-01-05