Authors
Pan Xie, Ying Zhang, Zhichao Xiao, Mengting Tan, Zhikui Luo, Fusen Peng
Published in
Discover oncology. Jul 17, 2026. Epub Jul 17, 2026.
Abstract
Entosis is a non-apoptotic form of cell-in-cell death implicated in tumor progression and immune evasion. However, the prognostic and immunological significance of entosis-related genes in head and neck squamous cell carcinoma (HNSCC) has not been systematically studied. This study aimed to construct and validate an entosis-anchored hybrid prognostic signature for HNSCC and to characterize its association with the tumor immune microenvironment and therapeutic response.
Gene expression and clinical data of 565 HNSCC patients from The Cancer Genome Atlas (TCGA) were used as the discovery cohort, randomly split into training (n = 396) and testing (n = 169) sets. A hybrid strategy integrating entosis pathway genes with genome-wide candidates was employed to construct a 14-gene prognostic signature via LASSO-Cox regression. External validation was performed in GSE65858, GSE41613, and CPTAC cohorts, with a fixed-effect meta-analysis synthesizing the results. Immune infiltration, immune checkpoint expression, TIDE-based immune evasion, drug sensitivity (oncoPredict/GDSC2 cell-line data), and a clinical nomogram were also evaluated.
The 14-gene entosis-anchored signature (ERS-14) comprised four entosis core genes (MYL2, CDKN2A, LAMP1, SPP1) and ten genome-wide prognostic genes. In the TCGA cohort, ERS-14 achieved a concordance index (C-index) of 0.703 and time-dependent AUC values of 0.737, 0.739, and 0.725 at 1, 3, and 5 years, respectively. Meta-analysis across external cohorts confirmed its prognostic value (HR = 1.551, 95% CI 1.147-2.096, p = 0.004, I² = 0%). Multivariate Cox regression demonstrated that ERS-14 was an independent predictor (HR = 4.362, p < 2 × 10⁻²⁰), and subgroup analysis revealed consistent prognostic performance across all 13 clinical subgroups tested. The high-risk group exhibited a T cell exclusion phenotype characterized by elevated cancer-associated fibroblast (CAF) scores (p = 0.008), downregulated immune checkpoints, and significantly increased resistance to cisplatin (p = 0.0001) and multiple targeted agents.
We developed and validated ERS-14, an entosis-anchored hybrid prognostic signature in HNSCC that predicts survival, identifies an immunosuppressive microenvironment driven by T cell exclusion, and reveals therapeutic vulnerabilities that may inform treatment selection.
PMID:
42469539
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 6
- Comments 0