MicroRNA Dysregulation and Non-Muscle-Invasive Bladder Cancer Prognosis

• Type of Material: Article
• Authors: Angeline S Andrew, Geisel School of Medicine at Dartmouth College; Margaret R Karagas, Geisel School of Medicine at Dartmouth College; Florian R Schroeck, Geisel School of Medicine at Dartmouth College; Carmen Marsit, Emory University; Alan R Schned, Geisel School of Medicine at Dartmouth College; Jason Pettus, Geisel School of Medicine at Dartmouth College; David A Armstrong, Geisel School of Medicine at Dartmouth College; John D Seigne, Geisel School of Medicine at Dartmouth College
• Language: English
• Date: 2019-04-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 American Association for Cancer Research.
• Final Published Version (URL): http://dx.doi.org/10.1158/1055-9965.EPI-18-0884
• Title of Journal or Parent Work: Cancer, Epidemiology, Biomarkers & Prevention
• Volume: 28
• Issue: 4
• Start Page: 782
• End Page: 788
• Grant/Funding Information: NCI Cancer Center Support Grant 5P30 CA023108-37; grant numbers R21CA182659, K07CA102327, and P42ES07373 from the National Cancer Institute, NIH, from the National Institute of Environmental Health Sciences, NIH
• Keywords: Public, Environmental & Occupational Health; Oncology; Science & Technology; RISK-FACTORS; EPIDEMIOLOGY; INHIBIT; Life Sciences & Biomedicine; KIDNEY
• Research Categories: Health Sciences, Oncology; Health Sciences, Epidemiology

Abstract

Background: The high rate of non-muscle–invasive bladder Results: miR-26b-5p was the top-ranking prognostic tumor cancer recurrence is a major challenge in patient management. tissue miRNA, with a time-to-recurrence HR 0.043 for levels miRNAs functionally regulate tumor cell proliferation and above versus below median, (P adj ¼ 0.0003). miR-26b-5p was invasion, and have strong potential as biomarkers because related to a dose-response reduction in tumor recurrence, and they are robust to degradation. The objective of this project was levels above the median were also associated with reduced to identify reproducible prognostic miRNAs in resected non-time-to-progression (P adj ¼ 0.02). We used two independent muscle–invasive bladder tumor tissue that are predictive of the longitudinal cohorts that included both low-grade and high-recurrent tumor phenotype. grade Ta and T1 tumors for validation and found a consistent Methods: We utilized patients diagnosed with primary non-relationship between miR-26b-5p and recurrence and muscle–invasive bladder cancer in three independent cohorts progression. for a biomarker discovery/validation approach. Baseline Conclusions: Our results suggest that miR-26b-5p levels tumor tissue from patients with the clinically challenging, may be prognostic for non-muscle–invasive bladder cancer non-muscle–invasive primary low stage (Ta), high grade, and recurrence, and can feasibly be assessed in baseline tumor T1 tumors (tumors extending into the lamina propria) com-tissue from a wide variety of clinical settings. prised the discovery cohort (n ¼ 38). We isolated the tumor Impact: Early identification of those non-muscle–invasive tissue RNA and assessed a panel of approximately 800 bladder tumor patients with refractory phenotypes would miRNAs. enable individualized treatment and surveillance.