title: Gene Expression Differences in Prostate Cancers between Young and Old Men.
abstract: Prostate cancer incidence is increasing in younger men. We investigated whether men diagnosed with Gleason 7 (3+4) T2 prostate cancer at younger ages (≤ 45 years, young cohort) had different mRNA and miRNA expression profiles than men diagnosed at older ages (71-74 years, older cohort). We identified differentially expressed genes (DEGs) related to tumor-normal differences between the cohorts. Subsequent pathway analysis of DEGs revealed that the young cohort had significantly more pronounced inflammatory and immune responses to tumor development compared to the older cohort. Further supporting a role of inflammation-induced immune-suppression in the development of early-onset prostate cancer, we observed significant up-regulation of CTLA4 and IDO1/TDO2 pathways in tumors of the young cohort. Moreover, over-expression of CTLA4 and IDO1 was significantly associated with biochemical recurrence. Our results provide clues on the mechanisms of tumor development and point to potential biomarkers for early detection and treatment for prostate cancer in young men.
authors.affiliation: Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Yuanchun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cellular and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Warden
authors.affiliation: Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Linda
authors.identifier: http://orcid.org/0000-0003-3628-2022
authors.initials: L
authors.lastname: Steele
authors.affiliation: Department of Cellular and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Xueli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M van
authors.initials: MV
authors.lastname: Iterson
authors.affiliation: Department of Cellular and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nelson
authors.affiliation: Department of Cellular and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Zheng
authors.identifier: http://orcid.org/0000-0002-1635-1556
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cellular and Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Yate-Ching
authors.initials: YC
authors.lastname: Yuan
authors.affiliation: Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, United States of America.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D060908:CTLA-4 Antigen / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009363:Neoplasm Proteins