Rohina Rubicz1, Shanshan Zhao1, Craig April2, Jonathan L Wright1,3, Suzanne Kolb1, Ilsa Coleman4, Daniel W Lin1,3, Peter S Nelson4,5,6, Elaine A Ostrander7, Ziding Feng8, Jian-Bing Fan2, Janet L Stanford1,9. 1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. 2. Illumina, Inc., San Diego, California. 3. Department of Urology, University of Washington School of Medicine, Seattle, Washington. 4. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington. 5. Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington. 6. Department of Medicine, University of Washington School of Medicine, Seattle, Washington. 7. Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland. 8. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas. 9. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
Abstract
BACKGROUND: Prostate cancer (PCa) is clinically and biologically heterogeneous, making it difficult to predict at detection whether it will take an indolent or aggressive disease course. Cell cycle-regulated genes may be more highly expressed in actively dividing cells, with transcript levels reflecting tumor growth rate. Here, we evaluated expression of cell cycle genes in relation to PCa outcomes in a population-based cohort. METHODS: Gene expression data were generated from tumor tissues obtained at radical prostatectomy for 383 population-based patients (12.3-years average follow-up). The overall mean and individual transcript levels of 30 selected cell cycle genes was compared between patients with no evidence of recurrence (73%) and those who recurred (27%) or died (7%) from PCa. RESULTS: The multivariate adjusted hazard ratio (HR) for a change from the 25th to 75th percentile of mean gene expression level (range 8.02-10.05) was 1.25 (95%CI 0.96-1.63; P = 0.10) for PCa recurrence risk, and did not vary substantially by Gleason score, TMPRSS2-ERG fusion status, or family history of PCa. For lethal PCa, the HR for a change (25th to 75th percentile) in mean gene expression level was 2.04 (95%CI 1.26-3.31; P = 0.004), adjusted for clinicopathological variables. The ROC curve for mean gene expression level alone (AUC = 0.740) did not perform as well as clinicopathological variables alone (AUC = 0.803) for predicting lethal PCa, and the addition of mean gene expression to clinicopathological variables did not substantially improve prediction (AUC = 0.827; P = 0.18). Higher TK1 expression was strongly associated with both recurrent (P = 6.7 × 10(-5)) and lethal (P = 6.4 × 10(-6)) PCa. CONCLUSIONS: Mean expression level for 30 selected cell cycle-regulated genes was unrelated to recurrence risk, but was associated with a twofold increase in risk of lethal PCa. However, gene expression had less discriminatory accuracy than clinical variables alone for predicting lethal events. Transcript levels for several genes in the panel were significantly overexpressed in lethal versus non-recurrent PCa.
BACKGROUND:Prostate cancer (PCa) is clinically and biologically heterogeneous, making it difficult to predict at detection whether it will take an indolent or aggressive disease course. Cell cycle-regulated genes may be more highly expressed in actively dividing cells, with transcript levels reflecting tumor growth rate. Here, we evaluated expression of cell cycle genes in relation to PCa outcomes in a population-based cohort. METHODS: Gene expression data were generated from tumor tissues obtained at radical prostatectomy for 383 population-based patients (12.3-years average follow-up). The overall mean and individual transcript levels of 30 selected cell cycle genes was compared between patients with no evidence of recurrence (73%) and those who recurred (27%) or died (7%) from PCa. RESULTS: The multivariate adjusted hazard ratio (HR) for a change from the 25th to 75th percentile of mean gene expression level (range 8.02-10.05) was 1.25 (95%CI 0.96-1.63; P = 0.10) for PCa recurrence risk, and did not vary substantially by Gleason score, TMPRSS2-ERG fusion status, or family history of PCa. For lethal PCa, the HR for a change (25th to 75th percentile) in mean gene expression level was 2.04 (95%CI 1.26-3.31; P = 0.004), adjusted for clinicopathological variables. The ROC curve for mean gene expression level alone (AUC = 0.740) did not perform as well as clinicopathological variables alone (AUC = 0.803) for predicting lethal PCa, and the addition of mean gene expression to clinicopathological variables did not substantially improve prediction (AUC = 0.827; P = 0.18). Higher TK1 expression was strongly associated with both recurrent (P = 6.7 × 10(-5)) and lethal (P = 6.4 × 10(-6)) PCa. CONCLUSIONS: Mean expression level for 30 selected cell cycle-regulated genes was unrelated to recurrence risk, but was associated with a twofold increase in risk of lethal PCa. However, gene expression had less discriminatory accuracy than clinical variables alone for predicting lethal events. Transcript levels for several genes in the panel were significantly overexpressed in lethal versus non-recurrent PCa.
Authors: A Naderi; A E Teschendorff; N L Barbosa-Morais; S E Pinder; A R Green; D G Powe; J F R Robertson; S Aparicio; I O Ellis; J D Brenton; C Caldas Journal: Oncogene Date: 2006-08-28 Impact factor: 9.867
Authors: Jack Cuzick; Gregory P Swanson; Gabrielle Fisher; Arthur R Brothman; Daniel M Berney; Julia E Reid; David Mesher; V O Speights; Elzbieta Stankiewicz; Christopher S Foster; Henrik Møller; Peter Scardino; Jorja D Warren; Jimmy Park; Adib Younus; Darl D Flake; Susanne Wagner; Alexander Gutin; Jerry S Lanchbury; Steven Stone Journal: Lancet Oncol Date: 2011-03 Impact factor: 41.316
Authors: Jay T Bishoff; Stephen J Freedland; Leah Gerber; Pierre Tennstedt; Julia Reid; William Welbourn; Markus Graefen; Zaina Sangale; Eliso Tikishvili; Jimmy Park; Adib Younus; Alexander Gutin; Jerry S Lanchbury; Guido Sauter; Michael Brawer; Steven Stone; Thorsten Schlomm Journal: J Urol Date: 2014-02-07 Impact factor: 7.450
Authors: Matthew R Cooperberg; Jeffry P Simko; Janet E Cowan; Julia E Reid; Azita Djalilvand; Satish Bhatnagar; Alexander Gutin; Jerry S Lanchbury; Gregory P Swanson; Steven Stone; Peter R Carroll Journal: J Clin Oncol Date: 2013-03-04 Impact factor: 44.544
Authors: Stephen J Freedland; Leah Gerber; Julia Reid; William Welbourn; Eliso Tikishvili; Jimmy Park; Adib Younus; Alexander Gutin; Zaina Sangale; Jerry S Lanchbury; Joseph K Salama; Steven Stone Journal: Int J Radiat Oncol Biol Phys Date: 2013-06-05 Impact factor: 7.038
Authors: Eva LaTulippe; Jaya Satagopan; Alex Smith; Howard Scher; Peter Scardino; Victor Reuter; William L Gerald Journal: Cancer Res Date: 2002-08-01 Impact factor: 12.701
Authors: J Cuzick; D M Berney; G Fisher; D Mesher; H Møller; J E Reid; M Perry; J Park; A Younus; A Gutin; C S Foster; P Scardino; J S Lanchbury; S Stone Journal: Br J Cancer Date: 2012-02-23 Impact factor: 7.640
Authors: Jennifer Cullen; Denise Young; Yongmei Chen; Michael Degon; James Farrell; Jason Sedarsky; Wagner Baptiste; Philip Rosen; Vladimir Tolstikov; Michael Kiebish; Jacob Kagan; Sudhir Srivastava; Huai-Ching Kuo; Joel T Moncur; Inger L Rosner; Niven Narain; Viatcheslav Akmaev; Gyorgy Petrovics; Albert Dobi; David G McLeod; Shiv Srivastava; Isabell A Sesterhenn Journal: Eur Urol Focus Date: 2017-03-11
Authors: Milan S Geybels; Jonathan L Wright; Marina Bibikova; Brandy Klotzle; Jian-Bing Fan; Shanshan Zhao; Ziding Feng; Elaine A Ostrander; Daniel W Lin; Peter S Nelson; Janet L Stanford Journal: Clin Epigenetics Date: 2016-09-15 Impact factor: 6.551