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

by Selleckchem | Nov 15 2023

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.

Comments:

The provided research summary discusses the role of Kinesin Family Member 18B (KIF18B) in Nasopharyngeal Carcinoma (NPC) and its potential implications for prognosis and treatment response. Here's a breakdown of the key findings and implications:

1. **KIF18B Overexpression and Prognosis:**
- KIF18B is overexpressed in NPC, and this overexpression is associated with unfavorable prognosis.
- KIF18B expression correlates with advanced tumor characteristics, including T classification, N classification, and tumor stage. This suggests that KIF18B may be involved in the progression of NPC.

2. **Functional Analysis:**
- Functional analysis of KIF18B in NPC indicates its involvement in multiple processes, including immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification, and therapeutic responses.

3. **Immune Infiltration:**
   - The study uses various algorithms and assays to analyze immune cell infiltration in NPC.
   - KIF18B expression is positively correlated with the infiltration of regulatory T cells (Tregs), which are known to suppress immune responses.
   - Conversely, the infiltration of CD8+ T cells and macrophages decreases in the high KIF18B expression group, suggesting immune evasion mechanisms.

4. **Intercellular Communication:**
- High KIF18B expression in malignant cells is associated with increased interactions in the intercellular communication network.
- KIF18B-expressing malignant cells appear to recruit Tregs by modulating cytokines, chemokines, and immune checkpoints, potentially contributing to immune suppression.

5. **EMT Regulation:**
- KIF18B influences epithelial-mesenchymal transition (EMT) in NPC by regulating genes associated with EMT, including ITGA6, VIM, and ZEB1/2.

6. **M6A Modification:**
- The study suggests that aberrant overexpression of KIF18B in NPC may be related to N6-methyladenosine (m6A) modification, involving "writer" and "reader" genes, as well as "eraser" genes.

7. **Treatment Response:**
- KIF18B high-expression group exhibits a higher Tumor Immune Dysfunction and Exclusion (TIDE) score, which implies a potential resistance to immunotherapy.
- The group also shows elevated IC50 values for commonly used chemotherapy drugs, such as gemcitabine, oxaliplatin, and 5-fluorouracil, suggesting potential resistance to chemotherapy.

8. **Conclusion:**
   - KIF18B is identified as a significant prognostic marker in NPC.
   - It appears to play a role in immune evasion, EMT, m6A modification, and treatment response.
   - KIF18B may serve as a predictor of response to both immunotherapy and chemotherapy in NPC.

These findings suggest that KIF18B may have a multifaceted role in NPC progression, affecting immune regulation, tumor characteristics, and treatment outcomes. Further research into the molecular mechanisms underlying these associations could lead to the development of targeted therapies for NPC patients with high KIF18B expression. Additionally, this research highlights the importance of personalized treatment approaches based on individual tumor characteristics.