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Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.
- Source :
-
Frontiers in immunology [Front Immunol] 2024 Apr 24; Vol. 15, pp. 1310376. Date of Electronic Publication: 2024 Apr 24 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood.<br />Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it.<br />Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC.<br />Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Tie, Zhu, Yu, Dou, Wang, Wang and Ni.)
- Subjects :
- Humans
Male
Biomarkers, Tumor genetics
Gene Expression Regulation, Neoplastic
Receptors, Antigen, B-Cell genetics
Receptors, Antigen, B-Cell metabolism
Receptors, Antigen, T-Cell genetics
Receptors, Antigen, T-Cell metabolism
Sequence Analysis, RNA
Transcriptome
Tumor Microenvironment immunology
Tumor Microenvironment genetics
Carcinogenesis genetics
Hypopharyngeal Neoplasms genetics
Hypopharyngeal Neoplasms pathology
Hypopharyngeal Neoplasms immunology
Single-Cell Analysis
Squamous Cell Carcinoma of Head and Neck genetics
Squamous Cell Carcinoma of Head and Neck immunology
Squamous Cell Carcinoma of Head and Neck pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38720887
- Full Text :
- https://doi.org/10.3389/fimmu.2024.1310376