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Published on: June 2, 2023
Low PTGDS Expression Facilitates HNSCC by Suppressing Programmed Cell Death and Reducing B Cell-Mediated Immune
Dan Tao1, Yuan Zhong1, Haoran Zhu2
1Department of Stomatology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, China, tzc.edu.cn.
Prostaglandin D2 synthase (PTGDS) helps head and neck cancer cells evade cell death. PTGDS may be a diagnostic marker and therapeutic target for improving HNSCC prognosis and immune response.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a major global health concern.
- Evasion of programmed cell death (PCD) is a key feature of HNSCC.
- The role of cancer-associated fibroblasts (CAFs) in HNSCC's resistance to PCD is not well understood.
Purpose of the Study:
- To investigate the mechanisms by which CAFs contribute to PCD resistance in HNSCC.
- To identify novel prognostic biomarkers and therapeutic targets within the CAF compartment of HNSCC.
Main Methods:
- Analysis of single-cell sequencing, TCGA, and spatial transcriptome data from HNSCC samples.
- Utilized Seurat for clustering, Monocle2 for pseudotemporal analysis, and random forest for prognostic gene assessment.
- Employed ssGSEA, CIBERSORT, gain-of-function assays, Western blotting, and immunohistochemistry for validation.
Main Results:
- Identified seven distinct CAF subsets with defined differentiation trajectories.
- Discovered 32 prognostic CAF-associated PCD regulators, highlighting PTGDS and SQLE.
- PTGDS was downregulated in HNSCC, correlated with better prognosis, and its overexpression inhibited tumor growth while promoting apoptosis and B cell-related immune responses via CXCL13.
Conclusions:
- PTGDS acts as a crucial regulator connecting CAF-mediated PCD resistance and B cell immune modulation in HNSCC.
- PTGDS demonstrates potential as a diagnostic biomarker and therapeutic target for HNSCC.
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