MZB1 marks a B-cell-associated stromal-immune microenvironment in cervical squamous cell carcinoma: a multi-omics...

Cervical squamous cell carcinoma (CSCC) is a common gynecologic malignancy with a heterogeneous tumor immune microenvironment (TIME). The role of MZB1, a B-cell-specific molecular chaperone, in CSCC remains poorly characterized.

We performed an integrative multi-omics analysis combining spatial proteomics, single-cell RNA sequencing, spatial transcriptomics and bulk transcriptomics to characterize MZB1 expression and its association with the TIME and patient prognosis. All spatial transcriptomics analyses were restricted to malignant regions.

Spatial proteomics revealed MZB1 enrichment in immune-rich regions. Single-cell analysis confirmed predominant MZB1 expression in B cells. Within malignant regions, MZB1-high spots showed significantly higher abundance of B cells (p = 5.04 × 10⁻²⁴), macrophages (p = 2.21 × 10⁻³²), dendritic cells (p = 2.83 × 10⁻²²), CD8+ T cells (p = 1.98 × 10⁻³), and CD4+ T cells (p = 1.24 × 10⁻³). In the TCGA cohort, MZB1 was upregulated in tumors and independently associated with favorable overall survival (HR = 0.894, p = 0.045). Differential expression analysis revealed that MZB1-high spots were characterized by ECM remodeling, BMP signaling, and complement activation (49 upregulated genes). Notably, MZB1-high tumors showed higher T-cell dysfunction/exclusion scores, indicating paradoxical immune evasion despite an immune-infiltrated phenotype.

This integrative analysis suggests MZB1 as a B-cell-specific marker of a stromal-immune microenvironment in CSCC. MZB1-high tumors are characterized by immune infiltration, ECM remodeling, immune checkpoint upregulation, and favorable prognosis. These hypothesis-generating findings suggest that MZB1 may serve as a candidate biomarker for identifying stromal-immune tumors in CSCC, warranting prospective clinical validation.