Prognostic value of the SPOP mutant genomic subclass in prostate cancer

Jonathan Shoag, Deli Liu, Xiaoyue Ma, Clara Oromendia, Paul Christos, Karla Ballman, Cynthia Angulo, Peter Y. Cai, Christopher Gaffney, Eric Klein, Jeffrey Karnes, Robert B. Den, Yang Liu, Elai Davicioni, Christopher E. Barbieri

Research output: Contribution to journalArticle

Abstract

Background: Speckle-type POZ protein (SPOP) mutation defines one of the dominant prostate cancer genomic subtypes, yet the impact of this mutation on clinical prognosis is unknown. Methods: We defined SPOP mutation status either by DNA sequencing or by transcriptional signature in a pooled retrospective multi-institutional cohort, the Decipher retrospective cohort, the Decipher Genomics Resource Information Database prospective cohort, and The Cancer Genome Atlas. Kaplan-Meier survival analysis and multivariable Cox models were used to assess the independent impact of SPOP mutation on survival, biochemical recurrence and time to metastasis. The Decipher retrospective cohort was also used to assess the impact of the addition of SPOP mutation status to a model predicting adverse pathology at prostatectomy which was then validated in the Decipher prospective cohort. Results: A fixed-effect model incorporating results from multivariable Cox regression including 5,811 subjects demonstrated that SPOP mutation was associated with a lower rate of adverse pathology at radical prostatectomy (odds ratios 0.57, 95% confidence interval 0.34–0.93), independent of preoperative prostate-specific antigen, age, and pathologic Gleason score. SPOP was not associated with biochemical recurrence, metastasis-free survival, or cancer-specific survival independent of pathologic information. The addition of SPOP status to prognostic models reclassified a large proportion of patients with the mutation (55%) into a favorable risk group when used to predict adverse pathology. Conclusion: While the clinical utility of delineating any single molecular alteration in prostate cancer remains unclear, these results illustrates the importance of genomic subtypes in prostate cancer behavior and potential role in prognostic tools.

Original languageEnglish (US)
Pages (from-to)418-422
Number of pages5
JournalUrologic Oncology: Seminars and Original Investigations
Volume38
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Genomic subtype
  • Prognosis
  • Prostate cancer
  • SPOP

ASJC Scopus subject areas

  • Oncology
  • Urology

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    Shoag, J., Liu, D., Ma, X., Oromendia, C., Christos, P., Ballman, K., Angulo, C., Cai, P. Y., Gaffney, C., Klein, E., Karnes, J., Den, R. B., Liu, Y., Davicioni, E., & Barbieri, C. E. (2020). Prognostic value of the SPOP mutant genomic subclass in prostate cancer. Urologic Oncology: Seminars and Original Investigations, 38(5), 418-422. https://doi.org/10.1016/j.urolonc.2020.02.011