Taken together, our findings outline a practical workflow for identifying and quantifying different CTC-states in OSCC, with platelet-associated CTCs emerging as the predominant population detected. These findings support the importance of incorporating phenotypic heterogeneity and platelet-associated tumour cell interactions into future liquid biopsy-based translational pathology research and clinical biomarker development in OSCC.
Multi-omics and tissue analyses identified VHL as the most consistent risk gene, supported by colocalization, TCGA HNSC transcriptomic validation (P < 0.01), and DepMap functional data. GEN1 and POU5F1 expression in salivary gland tissue also associated with OCC risk.ConclusionThis multilayer SMR study reveals causal links between DNA repair-related genes and OCC, highlighting VHL as a key driver and suggesting targets for early detection and precision therapy.
However, overexpression of snail family transcriptional repressor 2 (SNAI2) reversed the function of ITGA5 in regulating OSCC cell proliferation, invasion, migration, and EMT. In conclusion, our study suggests that ITGA5 is upregulated in HNSCC and associated with poor prognosis; functional studies indicate ITGA5 promotes OSCC proliferation and metastasis via SNAI2, indicating that ITGA5 may be a potential therapeutic target for OSCC.
2 days ago
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SNAI1 (Snail Family Transcriptional Repressor 1) • SNAI2 (Snail Family Transcriptional Repressor 2) • ITGA5 (Integrin Subunit Alpha 5)
Clinically, LAMC2 expression was significantly elevated in OSCC tissues from betel nut chewers, and arecoline treatment of OSCC cell lines induced LAMC2 upregulation, EMT, and enhanced migratory and invasive capacities in vitro. Collectively, our study delineates a malignant trajectory of epithelial cell progression, highlighting LAMC2+ EpiC6 as a key aggressive subpopulation orchestrated by EMT-related transcriptional regulators and extracellular matrix remodeling. These findings offer mechanistic insights and identify potential therapeutic targets to disrupt tumor-stroma interplay and mitigate disease progression.
Flow cytometric analysis of xenograft tumors revealed that IGF2BP2 knockdown altered macrophage-related immune features, including a reduced proportion of CD86+ M1-like tumor-associated macrophages. Collectively, these findings support an oncogenic role for IGF2BP2 in OSCC and suggest that IGF2BP2 is associated with MAPK signaling and macrophage-related immune features in OSCC.
2 days ago
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CD86 (CD86 Molecule) • IGF2BP2 (Insulin Like Growth Factor 2 MRNA Binding Protein 2)
Novel therapeutic modalities, including immune checkpoint inhibitors and peptide receptor radionuclide therapy, show preliminary promise but lack robust clinical validation. Given the rarity and heterogeneity of these tumors, multidisciplinary management and the establishment of multicenter registries are crucial for improving diagnostic accuracy, standardizing treatment strategies, and enhancing clinical outcomes.
Importantly, current findings remain heterogeneous and context-dependent, varying according to tumor site, HPV status, microbial burden, host immune composition, and methodological variability across studies. Although microbiome-informed biomarkers and therapeutic strategies are increasingly being explored, most remain at early experimental stages and require robust OSCC-specific mechanistic and clinical validation before translational implementation.
Our study demonstrates that ALKBH5 promotes cisplatin resistance in OSCC through m6A-dependent demethylation of FOXA1 transcripts, highlighting the ALKBH5-FOXA1 axis as a promising therapeutic target for overcoming this resistance.
In conclusion, integrating intratumoral, inner peritumoral, and outer peritumoral radiomic features (Rad All model) may provide more reliable predictive performance for postoperative recurrence in HER2-positive breast cancer compared with single-region radiomic models. The combined nomogram incorporating Rad All and clinical risk factors further improves predictive efficacy and may serve as a supplementary tool for clinical decision-making. SHAP analysis enhances model interpretability by identifying key predictive features. However, given the lack of independent external validation, the generalizability of our models needs to be further verified in future prospective multi-center studies.