南方医科大学学报

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (9): 2006-2018.doi: 10.12122/j.issn.1673-4254.2025.09.20

• • 上一篇    

MZB1基因在泛癌中的表达及其与免疫浸润及预后的关系

张瑜1(), 李海涛1, 潘玉卿2, 曹杰贤2, 翟丽1, 张曦1()   

  1. 1.云南省肿瘤医院//昆明医科大学第三附属医院医学检验科，云南 昆明 650118
    2.昆明医科大学第一附属医院医学检验科//云南省检验医学重点实验室//云南省医学检验临床医学研究中心，云南 昆明 650032
  • 收稿日期:2025-05-15 出版日期:2025-09-20 发布日期:2025-09-28
  • 通讯作者: 张曦 E-mail:15520858743@163.com;zhangxi@kmmu.edu.cn
  • 作者简介:张 瑜，硕士，检验师，E-mail: 15520858743@163.com
  • 基金资助:
    云南省教育厅科学研究基金项目(2024J0330);云南省教育厅科学研究基金项目(2025J0247);云南省应用基础研究计划(202101AY070001-165);云南省临床医学研究中心子课题(202102AA100063-06)

Pan-cancer analysis of MZB1 expression and its association with immune infiltration and clinical prognosis

Yu ZHANG1(), Haitao LI1, Yuqing PAN2, Jiexian CAO2, Li ZHAI1, Xi ZHANG1()   

  1. 1.Department of Clinical Laboratory, Cancer Hospital of Yunnan Province, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China
    2.Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Yunnan Key Laboratory of Laboratory Medicine, Yunnan Provincal Clinical Research Center for Laboratory Medicine, Kunming 650032, China
  • Received:2025-05-15 Online:2025-09-20 Published:2025-09-28
  • Contact: Xi ZHANG E-mail:15520858743@163.com;zhangxi@kmmu.edu.cn

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摘要：

目的 探讨边缘区B细胞及B1细胞特异性蛋白（MZB1）在泛癌中的表达水平及其与患者预后、肿瘤微环境的关系。 方法 利用UCSC数据库提取MZB1在33种癌症中的表达数据、临床病理参数和生存数据。利用R软件分析MZB1与临床分期、患者预后、免疫调节基因、免疫检查点基因、肿瘤干性、免疫细胞浸润、肿瘤突变负荷（TMB）以及微卫星不稳定性（MSI）的相关性，使用cBioPortal在线数据库分析MZB1在泛癌中基因突变情况，利用ROC曲线分析MZB1的癌症诊断价值，利用RT-qPCR和Western blotting检测MZB1在髓系白血病和肾癌中的表达，利用EdU法检测干扰MZB1后细胞的增殖情况。 结果 与正常组织相比，MZB1在肾透明细胞癌（KIRC）、乳腺浸润性癌（BRCA）、急性髓系白血病（LAML）等20种肿瘤中高表达（P<0.05），并且与多种肿瘤的TNM分期和临床分期以及部分肿瘤的总生存期（OS）和无进展生存期（PFS）相关（P<0.05）。在大多数肿瘤中，MZB1的表达与免疫调节基因（CCL4、CXCL10、CCL5、CCR4、CCR7、XCR1、MHC、IL-10、TGF-β）、免疫检查点基因（LAG3、TIGIT、BTLA、PDCD1、CTLA4）、肿瘤的干性指数、免疫细胞浸润（B细胞、CD4+T细胞、CD8+T细胞、中性粒细胞、巨噬细胞、树突状细胞等）、TMB、MSI相关（P<0.05）。此外，MZB1在泛癌中的基因突变类型以扩增为主，并且对皮肤黑色素瘤（SKCM）、肾透明细胞癌（KIRC）和头颈部鳞状细胞癌（HNSC）均有较高的诊断价值。RT-qPCR和Western blotting结果均显示在髓系白血病细胞（HL60、KG-1、U937、MV-4-11）和肾癌细胞（786-O、769-P、OSRC-2）中MZB1呈高表达（P<0.05），下调MZB1表达后可降低HL60和769-P的增殖水平。 结论 MZB1在多种肿瘤中高表达，其异常表达影响多种肿瘤的发生及预后，有望成为新的肿瘤标志物和免疫调节靶点。

关键词: MZB1, 泛癌分析, 免疫浸润, 预后, 治疗靶点

Abstract:

Objective To investigate the expression levels of marginal zone B and B1-cell-specific protein (MZB1) in pan-cancer and its association with patient prognosis and tumor microenvironment (TME). Methods MZB1 expression data, clinicopathological parameters, and survival data from 33 cancer types were extracted from the UCSC database for analyzing the correlations of MZB1 with clinical stage, patient prognosis, immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). MZB1 gene mutations in pan-cancer were assessed using cBioPortal online database, and the value of MZB1 for cancer diagnosis was evaluated using ROC curve analysis. MZB1 expression levels in myeloid leukemia and renal carcinoma cells were detected using RT-qPCR and Western blotting, and the effect of MZB1 knockdown on cell proliferation was examined using EdU assay. Results MZB1 was significantly overexpressed in 20 cancer types, including kidney renal clear cell carcinoma (KIRC), breast invasive carcinoma, and acute myeloid leukemia. Its expression was associated with TNM stage, clinical stage, overall survival, and progression-free survival in multiple cancers. In most tumors, MZB1 expression was correlated significantly with immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, TMB, and microsatellite instability. Gene amplification was the predominant mutation type of MZB1 in pan-cancer, and MZB1 showed high diagnostic value for skin cutaneous melanoma, KIRC, and head and neck squamous cell carcinoma. MZB1 was highly expressed in different myeloid leukemia cell lines and renal carcinoma cell lines, and MZB1 knockdown significantly suppressed the proliferation of HL60 and 769-P cells. Conclusion MZB1 is highly expressed in a variety of tumors, and its aberrant expression affects the occurrence and prognosis of many tumors, suggesting its potential as a novel tumor biomarker and immunomodulatory target.

Key words: marginal zone B and B1-cell-specific protein, pan-cancer analysis, immune infiltration, prognosis, therapeutic target