Cargando…

Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies

Despite significant advances in cancer diagnosis and treatment, osteosarcoma (OSA), an aggressive primary bone tumor, has eluded attempts at improving patient survival for many decades. The difficulty in managing OSA lies in its extreme genetic complexity, drug resistance, and heterogeneity, making...

Descripción completa

Detalles Bibliográficos
Autores principales: Nance, Rebecca L., Cooper, Sara J., Starenki, Dmytro, Wang, Xu, Matz, Brad, Lindley, Stephanie, Smith, Annette N., Smith, Ashley A., Bergman, Noelle, Sandey, Maninder, Koehler, Jey, Agarwal, Payal, Smith, Bruce F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031617/
https://www.ncbi.nlm.nih.gov/pubmed/35456486
http://dx.doi.org/10.3390/genes13040680
_version_ 1784692434731532288
author Nance, Rebecca L.
Cooper, Sara J.
Starenki, Dmytro
Wang, Xu
Matz, Brad
Lindley, Stephanie
Smith, Annette N.
Smith, Ashley A.
Bergman, Noelle
Sandey, Maninder
Koehler, Jey
Agarwal, Payal
Smith, Bruce F.
author_facet Nance, Rebecca L.
Cooper, Sara J.
Starenki, Dmytro
Wang, Xu
Matz, Brad
Lindley, Stephanie
Smith, Annette N.
Smith, Ashley A.
Bergman, Noelle
Sandey, Maninder
Koehler, Jey
Agarwal, Payal
Smith, Bruce F.
author_sort Nance, Rebecca L.
collection PubMed
description Despite significant advances in cancer diagnosis and treatment, osteosarcoma (OSA), an aggressive primary bone tumor, has eluded attempts at improving patient survival for many decades. The difficulty in managing OSA lies in its extreme genetic complexity, drug resistance, and heterogeneity, making it improbable that a single-target treatment would be beneficial for the majority of affected individuals. Precision medicine seeks to fill this gap by addressing the intra- and inter-tumoral heterogeneity to improve patient outcome and survival. The characterization of differentially expressed genes (DEGs) unique to the tumor provides insight into the phenotype and can be useful for informing appropriate therapies as well as the development of novel treatments. Traditional DEG analysis combines patient data to derive statistically inferred genes that are dysregulated in the group; however, the results from this approach are not necessarily consistent across individual patients, thus contradicting the basis of precision medicine. Spontaneously occurring OSA in the dog shares remarkably similar clinical, histological, and molecular characteristics to the human disease and therefore serves as an excellent model. In this study, we use transcriptomic sequencing of RNA isolated from primary OSA tumor and patient-matched normal bone from seven dogs prior to chemotherapy to identify DEGs in the group. We then evaluate the universality of these changes in transcript levels across patients to identify DEGs at the individual level. These results can be useful for reframing our perspective of transcriptomic analysis from a precision medicine perspective by identifying variations in DEGs among individuals.
format Online
Article
Text
id pubmed-9031617
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90316172022-04-23 Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies Nance, Rebecca L. Cooper, Sara J. Starenki, Dmytro Wang, Xu Matz, Brad Lindley, Stephanie Smith, Annette N. Smith, Ashley A. Bergman, Noelle Sandey, Maninder Koehler, Jey Agarwal, Payal Smith, Bruce F. Genes (Basel) Article Despite significant advances in cancer diagnosis and treatment, osteosarcoma (OSA), an aggressive primary bone tumor, has eluded attempts at improving patient survival for many decades. The difficulty in managing OSA lies in its extreme genetic complexity, drug resistance, and heterogeneity, making it improbable that a single-target treatment would be beneficial for the majority of affected individuals. Precision medicine seeks to fill this gap by addressing the intra- and inter-tumoral heterogeneity to improve patient outcome and survival. The characterization of differentially expressed genes (DEGs) unique to the tumor provides insight into the phenotype and can be useful for informing appropriate therapies as well as the development of novel treatments. Traditional DEG analysis combines patient data to derive statistically inferred genes that are dysregulated in the group; however, the results from this approach are not necessarily consistent across individual patients, thus contradicting the basis of precision medicine. Spontaneously occurring OSA in the dog shares remarkably similar clinical, histological, and molecular characteristics to the human disease and therefore serves as an excellent model. In this study, we use transcriptomic sequencing of RNA isolated from primary OSA tumor and patient-matched normal bone from seven dogs prior to chemotherapy to identify DEGs in the group. We then evaluate the universality of these changes in transcript levels across patients to identify DEGs at the individual level. These results can be useful for reframing our perspective of transcriptomic analysis from a precision medicine perspective by identifying variations in DEGs among individuals. MDPI 2022-04-13 /pmc/articles/PMC9031617/ /pubmed/35456486 http://dx.doi.org/10.3390/genes13040680 Text en © 2022 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
Nance, Rebecca L.
Cooper, Sara J.
Starenki, Dmytro
Wang, Xu
Matz, Brad
Lindley, Stephanie
Smith, Annette N.
Smith, Ashley A.
Bergman, Noelle
Sandey, Maninder
Koehler, Jey
Agarwal, Payal
Smith, Bruce F.
Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
title Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
title_full Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
title_fullStr Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
title_full_unstemmed Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
title_short Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies
title_sort transcriptomic analysis of canine osteosarcoma from a precision medicine perspective reveals limitations of differential gene expression studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031617/
https://www.ncbi.nlm.nih.gov/pubmed/35456486
http://dx.doi.org/10.3390/genes13040680
work_keys_str_mv AT nancerebeccal transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT coopersaraj transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT starenkidmytro transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT wangxu transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT matzbrad transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT lindleystephanie transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT smithannetten transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT smithashleya transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT bergmannoelle transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT sandeymaninder transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT koehlerjey transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT agarwalpayal transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies
AT smithbrucef transcriptomicanalysisofcanineosteosarcomafromaprecisionmedicineperspectiverevealslimitationsofdifferentialgeneexpressionstudies