title: Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Preethi
authors.initials: P
authors.lastname: Krishnan
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada.
authors.forename: Sunita
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Graham
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada.
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.|Cross Cancer Institute, Alberta Health Services, Edmonton, Alberta, Canada.
authors.forename: Sambasivarao
authors.initials: S
authors.lastname: Damaraju
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D011379:Prognosis; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D060565:Argonaute Proteins; C421088:PIWIL1 protein, human; D012313:RNA
keywords: PIWI; TCGA; breast cancer; piRNA; prognostic marker