title: Prognostic value of discs large homolog 7 transcript levels in prostate cancer.
abstract: Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia-regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p ≤ 0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP.
authors.affiliation: Stem Cell Laboratory, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America ; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America ; Division of Preventive and Occupational Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Gomez
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Farhad
authors.initials: F
authors.lastname: Kosari
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Jan-Marie
authors.initials: JM
authors.lastname: Munz
authors.affiliation: Stem Cell Laboratory, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Schreiber
authors.affiliation: Stem Cell Laboratory, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Gaylord J
authors.initials: GJ
authors.lastname: Knutson
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Ida
authors.affiliation: University of Mississippi Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Abdelouahid
authors.initials: A
authors.lastname: El Khattouti
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
authors.affiliation: Stem Cell Laboratory, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota, United States of America ; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America ; Division of Preventive and Occupational Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Stanimir
authors.initials: S
authors.lastname: Vuk-Pavlović
mesh_terms: D016022:Case-Control Studies; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D008297:Male; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012372:ROC Curve; D014158:Transcription, Genetic
chemical_list: C465041:DLGAP5 protein, human; D009363:Neoplasm Proteins