Multi-omics analysis reveals the association between elevated KIF18B expression and unfavorable prognosis, immune evasion, and regulatory T cell activation in nasopharyngeal carcinoma

Abstract

Background: Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. The expression profile and functions of kinesin family member 18B (KIF18B) remain unclear in NPC.

Methods: Bulk and single-cell transcriptome data for NPC were downloaded. KIF18B expression differences in NPC and normal tissues and its prognostic value were validated by immunohistochemistry and Cox model. We performed multi-faceted functional enrichment analysis on KIF18B. Immune infiltration was analyzed comprehensively by the CIBERSORT, EPIC, and quanTIseq algorithms and the BisqueRNA package and confirmed by immunofluorescence assay. The intercellular communication were investigated by the CellChat package. We explored the dynamics of KIF18B expression by pseudotime trajectory. M6A modification analysis rely on SRAMP platform. The treatment response were evaluated by Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore and IC50 value.

Results: KIF18B overexpression in NPC led to unfavorable prognosis, and significantly associated with advanced T, N, and stage classifications. Functional analysis demonstrated that KIF18B was involved in immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification and therapeutic responses. The deconvolution algorithm indicated that activated regulatory T cells (Tregs) had the strongest positive correlation with KIF18B among immune cells (R = 0.631). Validated by immunofluorescence assay, the high KIF18B expression group displayed a notable rise in Tregs infiltration, accompanied by a substantial decrease in the infiltration of CD8⁺ T cells and macrophages. In the intercellular communication network, malignant cells with high KIF18B expression implicated in more interactions, and activated and recruited Tregs by modulating cytokines, chemokines, and immune checkpoints. KIF18B was upregulated in more advanced malignant cells and influenced EMT by regulating ITGA6, VIM, and ZEB1/2. KIF18B expression was positively related to m6A "writer" and "reader" genes, and negatively related to "eraser" genes. The KIF18B high expression group exhibited a higher TIDE score and elevated IC50 values for the commonly used chemotherapy drugs, gemcitabine, oxaliplatin, and 5-fluorouracil.

Conclusion: KIF18B is a significant prognostic marker in NPC, and may modulate immune evasion and EMT. M6A modification may account for the aberrant overexpression of KIF18B in NPC. Furthermore, KIF18B may predict response to immunotherapy and chemotherapy.

Keywords: KIF18B; epithelial-mesenchymal transition; immune infiltration; intercellular communication; m6A modification; nasopharyngeal carcinoma; regulatory T cell.