Global Transcriptome Analysis of Formalin-Fixed Prostate Cancer Specimens Identifies Biomarkers of Disease Recurrence

• Type of Material: Article
• Authors: Qi Long, Emory University; Jianpeng Xu, Emory University; Adeboye Osunkoya, Emory University; Soma Sannigrahi, Emory University; Brent A. Johnson, Emory University; Wei Zhou, Emory University; Theresa Gillespie, Emory University; Jong Y. Park, University of South Florida; Robert K. Nam, University of Toronto; Linda Sugar, University of Toronto; Aleksandra Stanimirovic, University of Toronto; Arun K. Seth, University of Toronto; John Petros, Emory University; Carlos Moreno, Emory University
• Language: English
• Date: 2014-06-15
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2014 AACR.
• Final Published Version (URL): http://dx.doi.org/10.1158/0008-5472.CAN-13-2699
• Title of Journal or Parent Work: Cancer Research
• ISSN: 0008-5472
• Volume: 74
• Issue: 12
• Start Page: 3228
• End Page: 3237
• Grant/Funding Information: This research was supported by DOD grant W81XWH-010-1-0090, NIH R01CA106826, NIH U01 CA168449, NIH R03CA173770, NIH R03CA183006, R01CA128813, Canadian Cancer Society Research Institute Grant 019038, as well as NCI Cancer Center Support Grant P30CA138292 for the Winship Cancer Genomics Shared Resource and the Emory Integrated Genomics Core.
• Keywords: EXPRESSION; APOPTOSIS; CELLS; Life Sciences & Biomedicine; Oncology; GENE FUSIONS; PATHWAY; RADICAL PROSTATECTOMY; PROTEIN; PRIMARY GLEASON PATTERN; Science & Technology; ACTIVATION; MESSENGER-RNA
• Research Categories: Biology, Genetics; Biology, Biostatistics; Health Sciences, Oncology

Abstract

Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3K signaling, steroid metabolism, translation, chromatin modification, and transcription. Sixteen genes have been associated with cancer, with five specifically associated with prostate cancer (BTG2, IGFBP3, SIRT1, MXI1, and FDPS). Validation was performed on an independent publicly available dataset of 140 patients, where the new signature panel outperformed markers published previously in terms of predicting biochemical recurrence. Our work also identified differences in gene expression between Gleason pattern 4 + 3 and 3 + 4 tumors, including several genes involved in the epithelial-to-mesenchymal transition and developmental pathways. Overall, this study defines a novel biomarker panel that has the potential to improve the clinical management of prostate cancer.