Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer
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Preethi Krishnan1, Sunita Ghosh2,3, Kathryn Graham2,3, John R. Mackey2,3, Olga Kovalchuk4, Sambasivarao Damaraju1,3
1Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
2Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
3Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada
4Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada
Sambasivarao Damaraju, email: [email protected]
Keywords: piRNA, PIWI, breast cancer, prognostic marker, TCGA
Received: January 13, 2016 Accepted: April 28, 2016 Published: May 10, 2016
Piwi-interacting RNAs (piRNAs), whose role in germline maintenance has been established, are now also being classified as post-transcriptional regulators of gene expression in somatic cells. PIWI proteins, central to piRNA biogenesis, have been identified as genetic and epigenetic regulators of gene expression. piRNAs/PIWIs have emerged as potential biomarkers for cancer but their relevance to breast cancer has not been comprehensively studied. piRNAs and mRNAs were profiled from normal and breast tumor tissues using next generation sequencing and Agilent platforms, respectively. Gene targets for differentially expressed piRNAs were identified from mRNA expression dataset. piRNAs and PIWI genes were independently assessed for their prognostic significance (outcomes: Overall Survival, OS and Recurrence Free Survival, RFS). We discovered eight piRNAs as novel independent prognostic markers and their association with OS was confirmed in an external dataset (The Cancer Genome Atlas). Further, PIWIL3 and PIWIL4 genes showed prognostic relevance. 306 gene targets exhibited reciprocal relationship with piRNA expression. Cancer cell pathways such as apoptosis and cell signaling were the key Gene Ontology terms associated with the regulated gene targets. Overall, we have captured the entire cascade of events in a dysregulated piRNA pathway and have identified novel markers for breast cancer prognostication.
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