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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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 |
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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 |
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