Meta-analysis identifies transcriptomic and immune shifts in oral potentially malignant disorders

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Human cell Published May 5, 2026 Medically reviewed May 11, 2026 Study authors: Vasudevan Vaishnav, Siddappa Gangotri, Sam Reba Elsa, Madhumathi H K, Thomas Anela, Sunny Sumsum P, … PubMed ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Note the association between transcriptomic shifts and immune cell enrichment during oral dysplasia progression.

This meta-analysis synthesized data from five datasets to catalogue transcriptomic patterns and signaling processes across various stages of oral potentially malignant disorders, including high-grade dysplasia (HGD), low-grade dysplasia (LGD), and low-risk lesions (LRL). The study focused on identifying major signaling processes, infiltrating immune cell subtypes, and hub gene networks associated with disease progression.

The findings indicate that transitions from low-to-high-risk lesions involve changes in DNA replication and loss of cell adhesions, with a reported fold change of 1.5 (p < 0.05) converging on a hub panel of tumor promoters and suppressors. As lesions shift toward high-grade dysplasia, there is enhanced immune/cytokine signaling, with a hub-gene network driving metabolic regulation, immune evasion, and ECM-stroma interaction. In transformed lesions, the study noted a persistent immune-modulatory environment accompanied by a downregulation of interferon (IFN) signaling.

Regarding immune cell dynamics, the analysis identified specific enrichment of T regulatory cells and dendritic cells during the differentiation of dysplasia grades. Additionally, T helper cells were identified as specific to malignant transformation.

These molecular and immunological shifts represent potential milestones in the progression of oral potentially malignant disorders. While these associations offer insights for prognosis, prevention, and therapeutic intervention, the study identifies associations between transcriptomic and immune shifts and disease progression rather than direct causality.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

PMID42082814

View Original Abstract ↓

Early detection of potentially malignant and malignant lesions in the oral cavity is mandatory for reduction in oral cancer incidence, detection at an early stage and improving survival. The objective of this study was to catalogue the transcriptomic pattern across pre-cancerous stages, identify the major signalling processes, and infiltrating immune cell subtypes using the integrated, multi-dataset, meta-analysis approach. Following a search in the public databases, a total of five datasets were included in the study. The patient samples were stratified to identify the changes in high-grade dysplasia (HGD, moderate/severe dysplasia) as opposed to low-risk lesions (LRL, benign/OPMD) and low-grade dysplasia (LGD). Weighted gene co-expression network analysis (WGCNA; p < 0.05, |Correlation coefficient|:0.3) integrated with differential gene expression (DEG; p < 0.05, Fold change: 1.5) analysis revealed alterations in low-to-high-risk lesions included changes in DNA replication, loss of cell adhesions converging on a hub panel of tumor promoter/suppressors. The shift to high grade dysplasia was marked by enhanced immune/cytokine signalling with hub-gene network driving metabolic regulation, immune evasion, and ECM-stroma interaction. In transformed lesions, the immune-modulatory environment persisted, now accompanied by a notable downregulation of interferon (IFN) signalling. Interferon-inducible network and stemness induction were key hub gene networks. Digital cytometric analysis indicated specific enrichment of T regulatory cells and dendritic cells in differentiating the grades of dysplasia, while T helper cells were specific for malignant transformation. Collectively, these results indicate the role of immune surveillance during oral carcinogenesis. The distinct molecular/immunological shifts during dysplastic progression and malignant transformation represent critical milestones in oral potentially malignant disorder (OPMD) progression, offering actionable insights for prognosis, prevention, and therapeutic intervention.