PANoptosis-based HNSCPAN-index predicts prognosis and reveals DSCAM as a therapeutic target in head and neck squamous cell carcinoma
4 affiliations
- 1The 2nd Department of Head and Neck Surgery, Department of Oncoplastic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- 2Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- 3Operation Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- 4Department of Anesthesia, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
Abstract
Objective: To establish a prognostic PANoptosis-related gene signature in HNSCC and elucidate the role of Down syndrome cell adhesion molecule (DSCAM) in regulating tumor progression and immune evasion. Methods: Differential expression and prognostic analyses were performed to define HNSCC subtypes based on PANoptosis-related genes. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct the HNSCPAN-index, which stratified patients into high- and low-risk groups. The predictive performance of this index was validated in independent cohorts. Associations with immune infiltration, mutation profiles, and drug sensitivity were also examined. Functional validation of DSCAM was conducted through in vitro and in vivo experiments. Results: Six prognostically significant genes were identified and integrated into the HNSCPAN-index, which demonstrated independent prognostic value. Immunological landscape analysis showed that the low-risk group defined by the HNSCPAN-index was enriched in CD8+ T cells, follicular helper T cells, and memory-activated CD4+ T cells. Consistently, immune, stromal, and microenvironmental scores were significantly higher in the low-risk group. DSCAM knockdown suppressed proliferation and migration of HNSCC cell lines. Knockdown of DSCAM promotes PANoptosis by inhibiting the activity of the PI3K/AKT pathway. In vivo, DSCAM depletion inhibited tumor growth and enhanced CD8+ T cell infiltration. Conclusions: The HNSCPAN-index may serve as a potential biomarker for prognostic stratification and prediction of therapeutic responses in HNSCC.
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BibTeX
@article{feng2026panoptosisbased,
title = {{PANoptosis-based HNSCPAN-index predicts prognosis and reveals DSCAM as a therapeutic target in head and neck squamous cell carcinoma}},
author = {Yekai Feng and Yonghang Zhang and Haibo Ou and Qinglai Tang and Xiaojun Tang and Miao Zeng and Tao Chen and Yuming Zhang and Shisheng Li},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0344957},
url = {https://doi.org/10.1371/journal.pone.0344957},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PANoptosis-based HNSCPAN-index predicts prognosis and reveals DSCAM as a therapeutic target in head and neck squamous cell carcinoma
AU - Yekai Feng
AU - Yonghang Zhang
AU - Haibo Ou
AU - Qinglai Tang
AU - Xiaojun Tang
AU - Miao Zeng
AU - Tao Chen
AU - Yuming Zhang
AU - Shisheng Li
PY - 2026
DA - 2026/09/15
JO - PLOS One
DO - 10.1371/journal.pone.0344957
UR - https://doi.org/10.1371/journal.pone.0344957
AB - Objective: To establish a prognostic PANoptosis-related gene signature in HNSCC and elucidate the role of Down syndrome cell adhesion molecule (DSCAM) in regulating tumor progression and immune evasion. Methods: Differential expression and prognostic analyses were performed to define HNSCC subtypes based on PANoptosis-related genes. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct the HNSCPAN-index, which stratified patients into high- and low-risk groups. The predictive performance of this index was validated in independent cohorts. Associations with immune infiltration, mutation profiles, and drug sensitivity were also examined. Functional validation of DSCAM was conducted through in vitro and in vivo experiments. Results: Six prognostically significant genes were identified and integrated into the HNSCPAN-index, which demonstrated independent prognostic value. Immunological landscape analysis showed that the low-risk group defined by the HNSCPAN-index was enriched in CD8+ T cells, follicular helper T cells, and memory-activated CD4+ T cells. Consistently, immune, stromal, and microenvironmental scores were significantly higher in the low-risk group. DSCAM knockdown suppressed proliferation and migration of HNSCC cell lines. Knockdown of DSCAM promotes PANoptosis by inhibiting the activity of the PI3K/AKT pathway. In vivo, DSCAM depletion inhibited tumor growth and enhanced CD8+ T cell infiltration. Conclusions: The HNSCPAN-index may serve as a potential biomarker for prognostic stratification and prediction of therapeutic responses in HNSCC.
SN - 1932-6203
ER -