title: NF-κB gene signature predicts prostate cancer progression.
abstract: In many patients with prostate cancer, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage prostate cancer would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with prostate cancer progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse prostate cancer model when compared with Hi-Myc alone. Using the nonmalignant NF-κB-activated androgen-depleted mouse prostate, a NF-κB-activated recurrence predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with prostate cancer. This transgenic mouse model-derived gene signature provides a useful and unique molecular profile for human prostate cancer prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery.
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Renjie
authors.initials: R
authors.lastname: Jin
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Yull
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Authors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TennesseeAuthors' Affiliations: Department of Urologic Surgery and Vanderbilt Prostate Cancer Center; Division of Genetic Medicine, Department of Medicine; Departments of Cancer Biology and Medicine; and Division of Cancer Biostatistics, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee robert.matusik@vanderbilt.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Matusik
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha