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Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218829/ https://www.ncbi.nlm.nih.gov/pubmed/37240283 http://dx.doi.org/10.3390/ijms24108938 |
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author | Weusthof, Christopher Burkart, Sebastian Semmelmayer, Karl Stögbauer, Fabian Feng, Bohai Khorani, Karam Bode, Sebastian Plinkert, Peter Plath, Karim Hess, Jochen |
author_facet | Weusthof, Christopher Burkart, Sebastian Semmelmayer, Karl Stögbauer, Fabian Feng, Bohai Khorani, Karam Bode, Sebastian Plinkert, Peter Plath, Karim Hess, Jochen |
author_sort | Weusthof, Christopher |
collection | PubMed |
description | Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion. |
format | Online Article Text |
id | pubmed-10218829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102188292023-05-27 Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma Weusthof, Christopher Burkart, Sebastian Semmelmayer, Karl Stögbauer, Fabian Feng, Bohai Khorani, Karam Bode, Sebastian Plinkert, Peter Plath, Karim Hess, Jochen Int J Mol Sci Article Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion. MDPI 2023-05-18 /pmc/articles/PMC10218829/ /pubmed/37240283 http://dx.doi.org/10.3390/ijms24108938 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Weusthof, Christopher Burkart, Sebastian Semmelmayer, Karl Stögbauer, Fabian Feng, Bohai Khorani, Karam Bode, Sebastian Plinkert, Peter Plath, Karim Hess, Jochen Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma |
title | Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma |
title_full | Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma |
title_fullStr | Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma |
title_full_unstemmed | Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma |
title_short | Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma |
title_sort | establishment of a machine learning model for the risk assessment of perineural invasion in head and neck squamous cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218829/ https://www.ncbi.nlm.nih.gov/pubmed/37240283 http://dx.doi.org/10.3390/ijms24108938 |
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