Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas

Abstract The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors. However, many patients develop recurrence and die of their disease despite curative surgery. Underlying mechanisms leading to establishment of systemic disease after co...

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Autores principales:	Helen Pasternack, Christiane Kuempers, Mario Deng, Iris Watermann, Till Olchers, Mark Kuehnel, Danny Jonigk, Christian Kugler, Florian Stellmacher, Torsten Goldmann, Jutta Kirfel, Ole Ammerpohl, Sven Perner, Martin Reck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ff870a588214cb1a79a0bb41e304374
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spelling	oai:doaj.org-article:9ff870a588214cb1a79a0bb41e3043742021-12-02T14:49:43ZIdentification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas10.1038/s41598-021-89030-92045-2322https://doaj.org/article/9ff870a588214cb1a79a0bb41e3043742021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89030-9https://doaj.org/toc/2045-2322Abstract The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors. However, many patients develop recurrence and die of their disease despite curative surgery. Underlying mechanisms leading to establishment of systemic disease after complete resection are mostly unknown. We therefore aimed at identifying molecular signatures of resected lung adenocarcinomas associated with the risk of an early relapse. The study comprised 89 patients with totally resected stage IA–IIIA lung adenocarcinomas. Patients suffering from an early relapse within two years after surgery were compared to patients without a relapse in two years. Patients were clinically and molecular pathologically characterized. Tumor tissues were immunohistochemically analyzed for the expression of Ki67, CD45, CD4, CD8, PD1, PD-L1, PD-L2 and CD34, by Nanostring nCounter PanCancer Immune Profiling Panel as well as a comprehensive methylome profiling using the Infinium MethylationEPIC BeadChip. We detected differential DNA methylation patterns as well as significantly differentially expressed genes associated with an early relapse after complete resection. Especially, CD1A was identified as a potential biomarker, whose reduced expression is associated with an early relapse. These findings might help to develop biomarkers improving risk assessment and patient selection for adjuvant therapy as well as establish novel targeted therapeutic strategies.Helen PasternackChristiane KuempersMario DengIris WatermannTill OlchersMark KuehnelDanny JonigkChristian KuglerFlorian StellmacherTorsten GoldmannJutta KirfelOle AmmerpohlSven PernerMartin ReckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Helen Pasternack Christiane Kuempers Mario Deng Iris Watermann Till Olchers Mark Kuehnel Danny Jonigk Christian Kugler Florian Stellmacher Torsten Goldmann Jutta Kirfel Ole Ammerpohl Sven Perner Martin Reck Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
description	Abstract The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors. However, many patients develop recurrence and die of their disease despite curative surgery. Underlying mechanisms leading to establishment of systemic disease after complete resection are mostly unknown. We therefore aimed at identifying molecular signatures of resected lung adenocarcinomas associated with the risk of an early relapse. The study comprised 89 patients with totally resected stage IA–IIIA lung adenocarcinomas. Patients suffering from an early relapse within two years after surgery were compared to patients without a relapse in two years. Patients were clinically and molecular pathologically characterized. Tumor tissues were immunohistochemically analyzed for the expression of Ki67, CD45, CD4, CD8, PD1, PD-L1, PD-L2 and CD34, by Nanostring nCounter PanCancer Immune Profiling Panel as well as a comprehensive methylome profiling using the Infinium MethylationEPIC BeadChip. We detected differential DNA methylation patterns as well as significantly differentially expressed genes associated with an early relapse after complete resection. Especially, CD1A was identified as a potential biomarker, whose reduced expression is associated with an early relapse. These findings might help to develop biomarkers improving risk assessment and patient selection for adjuvant therapy as well as establish novel targeted therapeutic strategies.
format	article
author	Helen Pasternack Christiane Kuempers Mario Deng Iris Watermann Till Olchers Mark Kuehnel Danny Jonigk Christian Kugler Florian Stellmacher Torsten Goldmann Jutta Kirfel Ole Ammerpohl Sven Perner Martin Reck
author_facet	Helen Pasternack Christiane Kuempers Mario Deng Iris Watermann Till Olchers Mark Kuehnel Danny Jonigk Christian Kugler Florian Stellmacher Torsten Goldmann Jutta Kirfel Ole Ammerpohl Sven Perner Martin Reck
author_sort	Helen Pasternack
title	Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
title_short	Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
title_full	Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
title_fullStr	Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
title_full_unstemmed	Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
title_sort	identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9ff870a588214cb1a79a0bb41e304374
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_version_	1718389464456232960

Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas

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