Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma.

Autor: Islam S; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Gleber-Netto FO; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mulcahy CF; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Glaun MDE; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX 77030, USA., Srivastava S; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA., Hunt PJ; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA., Williams MD; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Barbon CE; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Spiotto M; Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Zhao W; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston (UTHealth Houston) School of Public Health, Houston, TX 77030, USA., Adebayo A; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Akhter S; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Xie T; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Debnath KC; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Sathishkumar HN; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Myers B; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA., Lothumalla S; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA., Yaman I; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Burks JK; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Leukemia and Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Gomez J; Department of Leukemia and Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Rao X; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang J; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Woodman K; Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mansour J; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.; Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Shreveport Medical Center, Shreveport, LA 71103, USA., Arenkiel B; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Osman KL; Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Missouri, Columbia, MO 65211, USA., Haxton C; Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Missouri, Columbia, MO 65211, USA., Lever TE; Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Missouri, Columbia, MO 65211, USA., Hutcheson KA; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Amit M; Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2024 Jul 31; Vol. 16 (758), pp. eabq5585. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1126/scitranslmed.abq5585
Abstrakt: The incidence of human papilloma virus-mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH + ) and CGRP + sensory-afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43 + ) and immature cholinergic (ChAT + DCX + ) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP + nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP + and cholinergic (ChAT + ) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP + and ChAT + neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.
Databáze: MEDLINE