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

doi:10.12122/j.issn.1673-4254.2025.09.20

Abstract

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

Yu ZHANG, Haitao LI, Yuqing PAN, Jiexian CAO, Li ZHAI, Xi ZHANG. Pan-cancer analysis of MZB1 expression and its association with immune infiltration and clinical prognosis[J]. Journal of Southern Medical University, 2025, 45(9): 2006-2018.

Figures/Tables 9

Tab.1 English abbreviations of relevant cancers in pan-cancer data

Cancer type abbreviation	Full name of cancer type
ACC	Adrenocortical carcinoma
BLCA	Bladder urothelial carcinoma
BRCA	Breast invasive carcinoma
CESC	Cervical squamous cell carcinoma and endocervical adenocarcinoma
CHOL	Cholangiocarcinoma
COAD	Colon adenocarcinoma
COADREAD	Colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma
ESCA	Esophageal carcinoma
GBM	Glioblastoma multiforme
GBMLGG	Glioma
HNSC	Head and neck squamous cell carcinoma
KICH	Kidney chromophobe
KIPAN	Pan-kidney cohort (kich+kirc+kirp)
KIRC	Kidney renal clear cell carcinoma
KIRP	Kidney renal papillary cell carcinoma
LAML	Acute myeloid leukemia
LGG	Brain lower grade glioma
LIHC	Liver hepatocellular carcinoma
LUAD	Lung adenocarcinoma
LUSC	Lung squamous cell carcinoma
MESO	Mesothelioma
OV	Ovarian serous cystadenocarcinoma
PAAD	Pancreatic adenocarcinoma
PCPG	Pheochromocytoma and paraganglioma
PRAD	Prostate adenocarcinoma
READ	Rectum adenocarcinoma
SARC	Sarcoma
STAD	Stomach adenocarcinoma
SKCM	Skin cutaneous melanoma
STES	Stomach and esophageal carcinoma
TGCT	Testicular germ cell tumors
THCA	Thyroid carcinoma
THYM	Thymoma
UCEC	Uterine corpus endometrial carcinoma
UCS	Uterine carcinosarcoma
WT	High-risk wilms tumor

Fig.1 Expression of MZB1 in pan-cancer. *P<0.05, **P<0.01, ****P<0.0001.

Fig.2 Relationship between MZB1 and tumor pathological stage. A-C: Relationship between MZB1 and tumor TNM stage. D: Relationship between MZB1 and tumor stage. *P<0.05, **P<0.01, ***P<0.001.

Fig.3 Effect of MZB1 on cancer prognosis. A-F: Kaplan-Meier survival curves of MZB1 expression in UVM, KIRC,LAML, SARC, SKCM, and HNSC. G, H: Prognostic analysis of the effect of MZB1 expression on overall survival (G) and progression-free survival (H).

Fig.4 Immunological characterization of MZB1 and correlation between MZB1 and tumor stemness. A: Relationship between MZB1 and immunomodulatory genes. B: Relationship between MZB1 and immune checkpoint genes. C: Relationship between MZB1 and tumor stemness indices.

Fig.5 Correlation between MZB1 and immune cell infiltration levels in pan-cancer. A: TIMER. B: IPS. C: xCELL. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig.6 Mutation analysis of MZB1 and its correlation with TMB and MSI. A. Mutation analysis of MZB1 in tumors. B: Correlation of MZB1 with tumor TMB. C: Correlation of MZB1 with tumor MSI.

Fig.7 Diagnostic value of MZB1 for HNSC (A), KIRC (B) and SKCM (C).

Fig. 8 In vitro validation of MZB1 expression and functional assays in leukemia and renal carcinoma cell lines. A-D: Expression of MZB1 in leukemia and renal carcinoma cell lines determined using RT-qPCR and Western blotting. E: Expression levels of MZB1 in HL60 and 769-P cells following MZB1 knockdown. F: Changes in cell proliferation capacity after MZB1 knockdown assessed using EdU assay (scale bar= 200 μm). **P<0.01, ***P<0.001 vs HS-5/HK-2/si-NC.

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