Cargando…

Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models

Xenografts are essential models for studying cancer biology and developing oncology drugs, and are more informative with omics data. Most reported xenograft proteomics projects directly profiled tumors comprising human cancer cells and mouse stromal cells, followed by computational algorithms for as...

Descripción completa

Detalles Bibliográficos
Autores principales: Shi, Zhaomei, Mao, Binchen, Chen, Xiaobo, Hao, Piliang, Guo, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035517/
https://www.ncbi.nlm.nih.gov/pubmed/36968139
http://dx.doi.org/10.1158/2767-9764.CRC-22-0431
_version_ 1784911431093714944
author Shi, Zhaomei
Mao, Binchen
Chen, Xiaobo
Hao, Piliang
Guo, Sheng
author_facet Shi, Zhaomei
Mao, Binchen
Chen, Xiaobo
Hao, Piliang
Guo, Sheng
author_sort Shi, Zhaomei
collection PubMed
description Xenografts are essential models for studying cancer biology and developing oncology drugs, and are more informative with omics data. Most reported xenograft proteomics projects directly profiled tumors comprising human cancer cells and mouse stromal cells, followed by computational algorithms for assigning peptides to human and mouse proteins. We evaluated the performance of three main algorithms by carrying out benchmark studies on a series of human and mouse cell line mixtures and a set of liver patient-derived xenograft (PDX) models. Our study showed that approximately half of the characterized peptides are common between human and mouse proteins, and their allocations to human or mouse proteins cannot be satisfactorily achieved by any algorithm. As a result, many human proteins are erroneously labeled as differentially expressed proteins (DEP) between samples from the same human cell line mixed with different percentages of mouse cells, and the number of such false DEPs increases superquadratically with the mouse cell percentage. When mouse stromal cells are not removed from PDX tumors, about 30%–40% of DEPs from pairwise comparisons of PDX models are false positives, and about 20% of real DEPs cannot be identified irrespective of the threshold for calling differential expression. In conclusion, our study demonstrated that it is advisable to separate human and mouse cells in xenograft tumors before proteomic profiling to obtain more accurate measurement of species-specific protein expression. SIGNIFICANCE: This study advocates the separate-then-run over the run-then-separate approach as a better strategy for more reliable proteomic profiling of xenografts.
format Online
Article
Text
id pubmed-10035517
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Association for Cancer Research
record_format MEDLINE/PubMed
spelling pubmed-100355172023-03-24 Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models Shi, Zhaomei Mao, Binchen Chen, Xiaobo Hao, Piliang Guo, Sheng Cancer Res Commun Research Article Xenografts are essential models for studying cancer biology and developing oncology drugs, and are more informative with omics data. Most reported xenograft proteomics projects directly profiled tumors comprising human cancer cells and mouse stromal cells, followed by computational algorithms for assigning peptides to human and mouse proteins. We evaluated the performance of three main algorithms by carrying out benchmark studies on a series of human and mouse cell line mixtures and a set of liver patient-derived xenograft (PDX) models. Our study showed that approximately half of the characterized peptides are common between human and mouse proteins, and their allocations to human or mouse proteins cannot be satisfactorily achieved by any algorithm. As a result, many human proteins are erroneously labeled as differentially expressed proteins (DEP) between samples from the same human cell line mixed with different percentages of mouse cells, and the number of such false DEPs increases superquadratically with the mouse cell percentage. When mouse stromal cells are not removed from PDX tumors, about 30%–40% of DEPs from pairwise comparisons of PDX models are false positives, and about 20% of real DEPs cannot be identified irrespective of the threshold for calling differential expression. In conclusion, our study demonstrated that it is advisable to separate human and mouse cells in xenograft tumors before proteomic profiling to obtain more accurate measurement of species-specific protein expression. SIGNIFICANCE: This study advocates the separate-then-run over the run-then-separate approach as a better strategy for more reliable proteomic profiling of xenografts. American Association for Cancer Research 2023-02-06 /pmc/articles/PMC10035517/ /pubmed/36968139 http://dx.doi.org/10.1158/2767-9764.CRC-22-0431 Text en © 2023 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by/4.0/This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
spellingShingle Research Article
Shi, Zhaomei
Mao, Binchen
Chen, Xiaobo
Hao, Piliang
Guo, Sheng
Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models
title Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models
title_full Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models
title_fullStr Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models
title_full_unstemmed Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models
title_short Mouse Stromal Cells Confound Proteomic Characterization and Quantification of Xenograft Models
title_sort mouse stromal cells confound proteomic characterization and quantification of xenograft models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035517/
https://www.ncbi.nlm.nih.gov/pubmed/36968139
http://dx.doi.org/10.1158/2767-9764.CRC-22-0431
work_keys_str_mv AT shizhaomei mousestromalcellsconfoundproteomiccharacterizationandquantificationofxenograftmodels
AT maobinchen mousestromalcellsconfoundproteomiccharacterizationandquantificationofxenograftmodels
AT chenxiaobo mousestromalcellsconfoundproteomiccharacterizationandquantificationofxenograftmodels
AT haopiliang mousestromalcellsconfoundproteomiccharacterizationandquantificationofxenograftmodels
AT guosheng mousestromalcellsconfoundproteomiccharacterizationandquantificationofxenograftmodels