Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma
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We developed a computational framework to reconstruct the non-coding transcriptome from crosssectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome. We generated a catalogue of PDA-associated lncRNAs. We showed that lncRNAs define molecular subtypes with biological and clinical significance. We identified lncRNAs in genomic regions with SCNA and single nucleotide polymorphisms associated with lifetime risk of PDA and associated with clinical outcome using genomic and clinical data in PDA. We found that loss of LINC00673 regulates the epithelial differentiation state in PDA cells, increases migratory capacity in vitro and in vivo, and results in loss of epithelial and gain of mesenchymal markers, both in vitro and in tumour samples. This finding is further reflected in poor clinical outcome in low LINC00673 tumours. We expect that the collection of PDA-associated lncRNAs will aid in the design of targeted therapies and may contribute to the development of improved diagnostic tools for PDA. The recent clinical approval of the first antisense therapy for human disease provides a viable, practical approach for leveraging this new understanding of cancer biology.
“Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma”
AUTHORS: Luis Arnes, Zhaoqi Liu, Jiguang Wang, Hans Carlo Maurer, Irina Sagalovskiy, Marta Sanchez-Martin, Nikhil Bommakanti, Diana C Garofalo, Dina A Balderes, Lori Sussel, Kenneth P Olive, Raul Rabadan
LINK TO PUBLICATION:
Gut.Published Online First: 10 February 2018. doi: 10.1136/gutjnl-2017-314353