Molecular characterization of the salivary adenoid cystic carcinoma immune landscape by anatomic subsites.

Autor: Tasoulas J; Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Schrank TP; Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Bharambe H; Department of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA., Mehta J; Department of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA., Johnson S; Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Divaris K; Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Hackman TG; Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sheth S; Division of Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA., Kirtane K; Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA., Hernandez-Prera JC; Department of Pathology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA., Chung CH; Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA., Yarbrough WG; Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ferrarotto R; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Issaeva N; Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Theocharis S; Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Amelio AL; Department of Otolaryngology-Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Antonio.Amelio@moffitt.org.; Department of Tumor Microenvironment and Metastasis, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. Antonio.Amelio@moffitt.org.; Department of Head and Neck-Endocrine Oncology, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA. Antonio.Amelio@moffitt.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jul 09; Vol. 14 (1), pp. 15821. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1038/s41598-024-66709-3
Abstrakt: Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4 + T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4 + T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.
(© 2024. The Author(s).)
Databáze: MEDLINE
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