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Chromosome 8q arm overexpression is associated with worse prostate cancer prognosis.
Alshalalfa, Mohammed; Nguyen, Tiffany T; Stopsack, Konrad H; Khan, Anwar; Franco, Idalid; Seldon, Crystal; Swami, Nishwant; Jin, William; Meiyappan, Karthik; Ton, Minh; Venstrom, Jeffrey M; Dee, Edward Christopher; Mahal, Brandon A.
Afiliación
  • Alshalalfa M; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL.
  • Nguyen TT; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL.
  • Stopsack KH; Harvard T.H. Chan School of Public Health, Boston, MA; Massachusetts General Hospital, Harvard Medical School, Boston, MA.
  • Khan A; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL.
  • Franco I; Department of Radiation Oncology, Dana Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.
  • Seldon C; Department of Radiation Oncology, University of Miami/Jackson Memorial Hospital, Miami, FL.
  • Swami N; Harvard T.H. Chan School of Public Health, Boston, MA; University of Massachusetts Chan Medical School, Worcester, MA.
  • Jin W; Department of Radiation Oncology, University of Miami/Jackson Memorial Hospital, Miami, FL.
  • Meiyappan K; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL.
  • Ton M; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL.
  • Venstrom JM; Genentech, San Francisco, CA.
  • Dee EC; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: deee1@mskcc.org.
  • Mahal BA; Department of Radiation Oncology, University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, FL. Electronic address: bmahal@med.miami.edu.
Urol Oncol ; 41(2): 106.e17-106.e23, 2023 02.
Article en En | MEDLINE | ID: mdl-36400666
OBJECTIVE: Chromosome 8q arm (chr8q) is the most amplified chromosomal segment in advanced metastatic castration-resistant prostate cancer after chXq12. These regions harbor important oncogenes driving prostate cancer progression, including MYC that plays a role in various hallmarks of cancer, including cell cycle progression and immune surveillance. Herein we characterize the co-expression patterns of chr8q genes and their clinical utility in more than 7,000 radical prostatectomy samples. MATERIALS AND METHODS: Copy Number alterations of 336 genes on chr8q21 to chr8q24 were extracted from 2 primary prostate cancer cohorts (TCGA, n = 492; MSK-primary, n = 856) and 3 metastatic prostate cancer cohorts (MSK-met, N = 432; MSK-mCSPC, N = 424; SU2CPNAS, n = 444) from cBioPortal. Expression data for the 336 genes was extracted from 6,135 radical prostatectomy samples from Decipher GRID registry. For survival analysis, patients were grouped into top 10% and top 25% by band expression and were compared with the remaining cohort. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: Genes on chr8q were highly co-amplified and co-expressed. Copy number alterations and overexpression of chr8q genes in primary disease were associated with higher Gleason scores, increased risk of metastases, and increased prostate cancer specific mortality. Additionally, our data demonstrated high expression of MYC alone was not associated with differences in metastases free survival while high expression of other chr8q bands was associated with decreased metastases free survival. By combining chr8q data with an established genomic classifier like Decipher, we were able to develop a new model that was better at predicting metastases than Decipher alone. CONCLUSIONS: Our findings highlight the clinical utility of chr8q data, which can be used to improve prognostication and risk prediction in localized prostate cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Brazo / Neoplasias de la Próstata Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Urol Oncol Asunto de la revista: NEOPLASIAS / UROLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Brazo / Neoplasias de la Próstata Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Urol Oncol Asunto de la revista: NEOPLASIAS / UROLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos