Cargando…

Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR

Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options with very low response rate. Lung cancer is the most common cause of cancer death worldwide. Therapies that target driver gene mutations (e.g. EGFR, ALK, ROS1) and checkpoint inhibitors such anti-PD-1 and...

Descripción completa

Detalles Bibliográficos
Autores principales: Alwithenani, Akram, Bethune, Drew, Castonguay, Mathieu, Drucker, Arik, Flowerdew, Gordon, Forsythe, Marika, French, Daniel, Fris, John, Greer, Wenda, Henteleff, Harry, MacNeil, Mary, Marignani, Paola, Morzycki, Wojciech, Plourde, Madelaine, Snow, Stephanie, Marcato, Paola, Xu, Zhaolin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101740/
https://www.ncbi.nlm.nih.gov/pubmed/33956842
http://dx.doi.org/10.1371/journal.pone.0251080
_version_ 1783689005947158528
author Alwithenani, Akram
Bethune, Drew
Castonguay, Mathieu
Drucker, Arik
Flowerdew, Gordon
Forsythe, Marika
French, Daniel
Fris, John
Greer, Wenda
Henteleff, Harry
MacNeil, Mary
Marignani, Paola
Morzycki, Wojciech
Plourde, Madelaine
Snow, Stephanie
Marcato, Paola
Xu, Zhaolin
author_facet Alwithenani, Akram
Bethune, Drew
Castonguay, Mathieu
Drucker, Arik
Flowerdew, Gordon
Forsythe, Marika
French, Daniel
Fris, John
Greer, Wenda
Henteleff, Harry
MacNeil, Mary
Marignani, Paola
Morzycki, Wojciech
Plourde, Madelaine
Snow, Stephanie
Marcato, Paola
Xu, Zhaolin
author_sort Alwithenani, Akram
collection PubMed
description Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options with very low response rate. Lung cancer is the most common cause of cancer death worldwide. Therapies that target driver gene mutations (e.g. EGFR, ALK, ROS1) and checkpoint inhibitors such anti-PD-1 and PD-L1 immunotherapies are being used to treat lung cancer patients. Identification of correlations between driver mutations and PD-L1 expression will allow for the best management of patient treatment. 851 cases of non-small cell lung cancer cases were profiled for the presence of biomarkers EGFR, KRAS, BRAF, and PIK3CA mutations by SNaPshot/sizing genotyping. Immunohistochemistry was used to identify the protein expression of ALK and PD-L1. Total PD-L1 mRNA expression (from unsorted tumor samples) was quantified by RT-qPCR in a sub-group of the cohort to assess its correlation with PD-L1 protein level in tumor cells. Statistical analysis revealed correlations between the presence of the mutations, PD-L1 expression, and the pathological data. Specifically, increased PD-L1 expression was associated with wildtype EGFR and vascular invasion, and total PD-L1 mRNA levels correlated weakly with protein expression on tumor cells. These data provide insights into driver gene mutations and immune checkpoint status in relation to lung cancer subtypes and suggest that RT-qPCR is useful for assessing PD-L1 levels.
format Online
Article
Text
id pubmed-8101740
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-81017402021-05-17 Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR Alwithenani, Akram Bethune, Drew Castonguay, Mathieu Drucker, Arik Flowerdew, Gordon Forsythe, Marika French, Daniel Fris, John Greer, Wenda Henteleff, Harry MacNeil, Mary Marignani, Paola Morzycki, Wojciech Plourde, Madelaine Snow, Stephanie Marcato, Paola Xu, Zhaolin PLoS One Research Article Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options with very low response rate. Lung cancer is the most common cause of cancer death worldwide. Therapies that target driver gene mutations (e.g. EGFR, ALK, ROS1) and checkpoint inhibitors such anti-PD-1 and PD-L1 immunotherapies are being used to treat lung cancer patients. Identification of correlations between driver mutations and PD-L1 expression will allow for the best management of patient treatment. 851 cases of non-small cell lung cancer cases were profiled for the presence of biomarkers EGFR, KRAS, BRAF, and PIK3CA mutations by SNaPshot/sizing genotyping. Immunohistochemistry was used to identify the protein expression of ALK and PD-L1. Total PD-L1 mRNA expression (from unsorted tumor samples) was quantified by RT-qPCR in a sub-group of the cohort to assess its correlation with PD-L1 protein level in tumor cells. Statistical analysis revealed correlations between the presence of the mutations, PD-L1 expression, and the pathological data. Specifically, increased PD-L1 expression was associated with wildtype EGFR and vascular invasion, and total PD-L1 mRNA levels correlated weakly with protein expression on tumor cells. These data provide insights into driver gene mutations and immune checkpoint status in relation to lung cancer subtypes and suggest that RT-qPCR is useful for assessing PD-L1 levels. Public Library of Science 2021-05-06 /pmc/articles/PMC8101740/ /pubmed/33956842 http://dx.doi.org/10.1371/journal.pone.0251080 Text en © 2021 Alwithenani et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Alwithenani, Akram
Bethune, Drew
Castonguay, Mathieu
Drucker, Arik
Flowerdew, Gordon
Forsythe, Marika
French, Daniel
Fris, John
Greer, Wenda
Henteleff, Harry
MacNeil, Mary
Marignani, Paola
Morzycki, Wojciech
Plourde, Madelaine
Snow, Stephanie
Marcato, Paola
Xu, Zhaolin
Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR
title Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR
title_full Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR
title_fullStr Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR
title_full_unstemmed Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR
title_short Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR
title_sort profiling non-small cell lung cancer reveals that pd-l1 is associated with wild type egfr and vascular invasion, and immunohistochemistry quantification of pd-l1 correlates weakly with rt-qpcr
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101740/
https://www.ncbi.nlm.nih.gov/pubmed/33956842
http://dx.doi.org/10.1371/journal.pone.0251080
work_keys_str_mv AT alwithenaniakram profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT bethunedrew profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT castonguaymathieu profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT druckerarik profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT flowerdewgordon profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT forsythemarika profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT frenchdaniel profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT frisjohn profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT greerwenda profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT henteleffharry profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT macneilmary profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT marignanipaola profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT morzyckiwojciech profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT plourdemadelaine profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT snowstephanie profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT marcatopaola profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr
AT xuzhaolin profilingnonsmallcelllungcancerrevealsthatpdl1isassociatedwithwildtypeegfrandvascularinvasionandimmunohistochemistryquantificationofpdl1correlatesweaklywithrtqpcr