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Background <p>Head and neck squamous cell carcinoma (HNSCC) is a prevalent and aggressive cancer with poor prognosis despite advancements in treatment. The immune system plays a crucial role in HNSCC progression, yet the specific mechanisms linking immune cells to tumor development remain poorly understood. Coiled-coil domain-containing protein 86 (CCDC86) has been implicated in immune dysregulation, but its role in HNSCC has not been explored. This study investigates the expression of CCDC86 in HNSCC, its association with immune infiltration, and its potential as a prognostic biomarker.</p> Methods <p>This study integrates single-cell RNA sequencing (scRNA-seq), The Cancer Genome Atlas (TCGA) data, and Mendelian randomization (MR) analysis. scRNA-seq datasets from normal oral mucosa and HNSCC tissues were used to analyze CCDC86 expression in different cell populations. TCGA data were employed to assess the correlation between CCDC86 expression and clinicopathological features of HNSCC. MR analysis was conducted to explore the causal relationship between CCDC86 and immune cell phenotypes in HNSCC.</p> Results <p>CCDC86 was significantly overexpressed in HNSCC tissues compared to normal tissues. High expression of CCDC86 was associated with poor prognosis, correlating with histological grade, clinical stage, and survival outcomes. Gene ontology (GO) and KEGG pathway analyses revealed that CCDC86 is involved in immune cell activation and receptor complex assembly. A negative correlation between CCDC86 expression and immune infiltration, especially in dendritic cells (DCs) and T cells, was observed. MR analysis confirmed a causal relationship between CCDC86 expression and HNSCC risk, with a notable effect on immune cell populations, particularly myeloid DCs.</p> Conclusion <p>CCDC86 expression is upregulated in HNSCC and is associated with adverse clinicopathological features and poor prognosis. CCDC86 modulates immune cell infiltration, particularly inhibiting the function of conventional dendritic cells. These findings suggest that CCDC86 could serve as a prognostic biomarker and a potential therapeutic target for HNSCC treatment.</p>

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CCDC86 modulates immune cell infiltration and disease progression in head and neck squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月30日

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  • Fei He,
  • Yang Liu,
  • Xinjian Zhang,
  • Rongrong Zhang,
  • Jiaxuan Qiu,
  • Sijia Na

摘要

Background

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and aggressive cancer with poor prognosis despite advancements in treatment. The immune system plays a crucial role in HNSCC progression, yet the specific mechanisms linking immune cells to tumor development remain poorly understood. Coiled-coil domain-containing protein 86 (CCDC86) has been implicated in immune dysregulation, but its role in HNSCC has not been explored. This study investigates the expression of CCDC86 in HNSCC, its association with immune infiltration, and its potential as a prognostic biomarker.

Methods

This study integrates single-cell RNA sequencing (scRNA-seq), The Cancer Genome Atlas (TCGA) data, and Mendelian randomization (MR) analysis. scRNA-seq datasets from normal oral mucosa and HNSCC tissues were used to analyze CCDC86 expression in different cell populations. TCGA data were employed to assess the correlation between CCDC86 expression and clinicopathological features of HNSCC. MR analysis was conducted to explore the causal relationship between CCDC86 and immune cell phenotypes in HNSCC.

Results

CCDC86 was significantly overexpressed in HNSCC tissues compared to normal tissues. High expression of CCDC86 was associated with poor prognosis, correlating with histological grade, clinical stage, and survival outcomes. Gene ontology (GO) and KEGG pathway analyses revealed that CCDC86 is involved in immune cell activation and receptor complex assembly. A negative correlation between CCDC86 expression and immune infiltration, especially in dendritic cells (DCs) and T cells, was observed. MR analysis confirmed a causal relationship between CCDC86 expression and HNSCC risk, with a notable effect on immune cell populations, particularly myeloid DCs.

Conclusion

CCDC86 expression is upregulated in HNSCC and is associated with adverse clinicopathological features and poor prognosis. CCDC86 modulates immune cell infiltration, particularly inhibiting the function of conventional dendritic cells. These findings suggest that CCDC86 could serve as a prognostic biomarker and a potential therapeutic target for HNSCC treatment.