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doi:10.22028/D291-34882
Titel: | Prognostic Gene Signature for Squamous Cell Carcinoma with a Higher Risk for Treatment Failure and Accelerated MEK-ERK Pathway Activity |
VerfasserIn: | Feng, Bohai Wang, Kai Herpel, Esther Plath, Michaela Weichert, Wilko Freier, Kolja Zaoui, Karim Hess, Jochen |
Sprache: | Englisch |
Titel: | Cancers |
Bandnummer: | 13 |
Heft: | 20 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | HNSCC squamous cell carcinoma prognostic classifier genetic and epigenetic alterations multi-omics analysis MEK inhibitors MEK-ERK signaling |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Squamous cell carcinoma (SCC) is the most prevalent histological type of human cancer, including head and neck squamous cell carcinoma (HNSCC). However, reliable prognostic gene signatures for SCC and underlying genetic and/or epigenetic principles are still unclear. We identified 37 prognostic candidate genes by best cutoff computation based on survival in a pan-SCC cohort (n = 1334) of The Cancer Genome Atlas (TCGA), whose expression stratified not only the pan-SCC cohort but also independent HNSCC validation cohorts into three distinct prognostic subgroups. The most relevant prognostic genes were prioritized by a Least Absolute Shrinkage and Selection Operator Cox regression model and were used to identify subgroups with high or low risks for unfavorable survival. An integrative analysis of multi-omics data identified FN1, SEMA3A, CDH2, FBN1, COL5A1, and ADAM12 as key nodes in a regulatory network related to the prognostic phenotype. An in-silico drug screen predicted two MEK inhibitors (Trametinib and Selumetinib) as effective compounds for high-risk SCC based on the Cancer Cell Line Encyclopedia, which is supported by a higher p-MEK1/2 immunohistochemical staining of high-risk HNSCC. In conclusion, our data identified a molecular classifier for high-risk HNSCC as well as other SCC patients, who might benefit from treatment with MEK inhibitors. |
DOI der Erstveröffentlichung: | 10.3390/cancers13205182 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-348826 hdl:20.500.11880/31907 http://dx.doi.org/10.22028/D291-34882 |
ISSN: | 2072-6694 |
Datum des Eintrags: | 27-Okt-2021 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Material |
In Beziehung stehendes Objekt: | https://www.mdpi.com/2072-6694/13/20/5182/s1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Zahn-, Mund- und Kieferheilkunde |
Professur: | M - Prof. Dr. Kolja Freier |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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cancers-13-05182-v2.pdf | 6,37 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons