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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Public Library of Science (PLoS)
2021
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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) |
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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 |
work_keys_str_mv |
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