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AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck

X. Gu, L. Wang, L. Boldrup, PJ. Coates, R. Fahraeus, N. Sgaramella, T. Wilms, K. Nylander,

. 2019 ; 11 (3) : . [pub] 20190311

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19013265

A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan⁻Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.

Citace poskytuje Crossref.org

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$a A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan⁻Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.
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$a Boldrup, Linda $u Department of Medical Biosciences/Pathology, Umeå University, 90185 Umeå, Sweden. linda.boldrup@umu.se.
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$a Coates, Philip J $u RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic. philip.coates@mou.cz.
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$a Fahraeus, Robin $u Department of Medical Biosciences/Pathology, Umeå University, 90185 Umeå, Sweden. robin.fahraeus@inserm.fr. RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic. robin.fahraeus@inserm.fr. Équipe Labellisée Ligue Contre le Cancer, INSERM UMRS1162, Institut de Génétique Moléculaire, Université Paris 7, IUH Hôpital St. Louis, 75010 Paris, France. robin.fahraeus@inserm.fr.
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$a Sgaramella, Nicola $u Department of Medical Biosciences/Pathology, Umeå University, 90185 Umeå, Sweden. sgaramellanicola12@gmail.com.
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$a Wilms, Torben $u Department of Clinical Sciences/ENT, Umeå University, 90185 Umeå, Sweden. Torben.Wilms@vll.se.
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$a Nylander, Karin $u Department of Medical Biosciences/Pathology, Umeå University, 90185 Umeå, Sweden. karin.nylander@umu.se.
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