Objective:

To evaluate the clinical and biological relevance of ORC6 in oral squamous cell carcinoma (OSCC) and its association with immune features.

Approach:

• Study Design: Integrated bulk transcriptomic data, single-cell transcriptomic profiling, immune-context analyses, and in vitro ORC6-knockdown assays.
• Data Sources: Utilized public transcriptomic datasets from TCGA, GEO, GTEx, and GSE181919, focusing on a strictly defined OSCC cohort.
• Experimental Validation: Conducted ORC6 knockdown in CAL27 cells to assess effects on cell growth, migration, invasion, and antigen presentation.

Key Findings:

• ORC6 is upregulated in OSCC tissues and cell lines, correlating with adverse clinicopathological features and poorer survival outcomes.
• High ORC6 expression is associated with a replication-active state in malignant epithelial cells, characterized by activation of DNA-replication and cell-cycle programs.
• ORC6 expression inversely correlates with immune-related features, including cytolytic activity and antigen-presentation signatures.

Interpretation:

ORC6 is linked to a malignant epithelial state in OSCC associated with reduced immune features, particularly in antigen presentation.

Limitations:

• The study primarily focuses on OSCC, which may limit the applicability of findings to other head and neck cancers.
• Further functional immune-recognition studies and independent clinical validation are necessary to confirm these findings.

Conclusion:

ORC6 is associated with a replication-active malignant state in OSCC and correlates with low immune features, warranting further investigation.