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Exploring PANoptosis in head and neck cancer: A novel approach to cancer therapy
Li Wang1, Baisheng Lin1, Feixiang Wang2
1Department of Radiation Oncology, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China.
Abstract:
PANoptosis is a newly discovered complex programmed cell death (PCD) form. In the field of cancer research, PANoptosis is involved in multiple cell death pathways that affect tumor cell survival, proliferation, and response to treatment, serving as an innovative strategy for cancer therapy. Endocrine-disrupting chemicals (EDCs) impact the endocrine system, including cancer. However, research on their influence on head and neck carcinoma (HNSC) through PANoptosis genes remains limited. This study utilises transcriptomic and clinical data related to HNSC from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. We developed a risk model based on PANoptosis-related genes through LASSO Cox regression analysis. Finally, we utilized a Sankey diagram to depict the relationships between EDCs and key genes, identifying DSCAM, IL-6, and SYCP2 as critical predictors of HNSC PANoptosis. These essential genes identified 214 EDCs potentially influencing HNSC, including 3 (Aroclor 1242, Pentachlorobenzene, and Propanil) previously unreported to HNSC. These findings elucidate novel relationships between PANoptosis-related genes mediated by EDCs and the pathogenesis of HNSC.
Insights
This study reveals how endocrine-disrupting chemicals (EDCs) influence head and neck squamous cell carcinoma (HNSC) through PANoptosis genes. It identifies key genes and EDCs, offering new insights into HNSC pathogenesis.
Area of Science:
- Oncology
- Cell Death Research
- Environmental Health
Background:
- PANoptosis, a complex programmed cell death (PCD) pathway, is crucial in cancer therapy by affecting tumor survival and treatment response.
- Endocrine-disrupting chemicals (EDCs) are known to impact cancer development, but their specific role in head and neck squamous cell carcinoma (HNSC) via PANoptosis genes is underexplored.
Purpose of the Study:
- To investigate the association between EDCs and PANoptosis-related genes in HNSC.
- To develop a predictive risk model for HNSC based on PANoptosis genes.
- To identify novel EDCs and key genes implicated in HNSC pathogenesis.
Main Methods:
- Utilized transcriptomic and clinical data from TCGA and GEO databases for HNSC.
- Applied LASSO Cox regression analysis to construct a risk model using PANoptosis-related genes.
- Employed Sankey diagrams to visualize relationships between EDCs and identified key genes (DSCAM, IL-6, SYCP2).
Main Results:
- A risk model was developed, identifying DSCAM, IL-6, and SYCP2 as critical predictors of PANoptosis in HNSC.
- 214 EDCs were found to potentially influence HNSC, including three previously unreported (Aroclor 1242, Pentachlorobenzene, Propanil).
- Established novel links between EDC-mediated PANoptosis pathways and HNSC development.
Conclusions:
- DSCAM, IL-6, and SYCP2 are key PANoptosis-related genes in HNSC, influenced by various EDCs.
- This research highlights previously unrecognized EDCs impacting HNSC, suggesting new therapeutic and preventative strategies.
- The findings provide a deeper understanding of the interplay between environmental factors, cell death mechanisms, and HNSC pathogenesis.
