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...

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Autores principales: Akram Alwithenani, Drew Bethune, Mathieu Castonguay, Arik Drucker, Gordon Flowerdew, Marika Forsythe, Daniel French, John Fris, Wenda Greer, Harry Henteleff, Mary MacNeil, Paola Marignani, Wojciech Morzycki, Madelaine Plourde, Stephanie Snow, Paola Marcato, Zhaolin Xu
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:e3c4b71be1604259a8c3660958c74ff82021-11-25T05:54:18ZProfiling 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.1932-620310.1371/journal.pone.0251080https://doaj.org/article/e3c4b71be1604259a8c3660958c74ff82021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251080https://doaj.org/toc/1932-6203Most 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.Akram AlwithenaniDrew BethuneMathieu CastonguayArik DruckerGordon FlowerdewMarika ForsytheDaniel FrenchJohn FrisWenda GreerHarry HenteleffMary MacNeilPaola MarignaniWojciech MorzyckiMadelaine PlourdeStephanie SnowPaola MarcatoZhaolin XuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251080 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Akram Alwithenani
Drew Bethune
Mathieu Castonguay
Arik Drucker
Gordon Flowerdew
Marika Forsythe
Daniel French
John Fris
Wenda Greer
Harry Henteleff
Mary MacNeil
Paola Marignani
Wojciech Morzycki
Madelaine Plourde
Stephanie Snow
Paola Marcato
Zhaolin Xu
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.
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 article
author Akram Alwithenani
Drew Bethune
Mathieu Castonguay
Arik Drucker
Gordon Flowerdew
Marika Forsythe
Daniel French
John Fris
Wenda Greer
Harry Henteleff
Mary MacNeil
Paola Marignani
Wojciech Morzycki
Madelaine Plourde
Stephanie Snow
Paola Marcato
Zhaolin Xu
author_facet Akram Alwithenani
Drew Bethune
Mathieu Castonguay
Arik Drucker
Gordon Flowerdew
Marika Forsythe
Daniel French
John Fris
Wenda Greer
Harry Henteleff
Mary MacNeil
Paola Marignani
Wojciech Morzycki
Madelaine Plourde
Stephanie Snow
Paola Marcato
Zhaolin Xu
author_sort Akram Alwithenani
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_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_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_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.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/e3c4b71be1604259a8c3660958c74ff8
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