SPINK1 Defines a Molecular Subtype of Prostate Cancer in Men with More Rapid Progression in an at Risk, Natural History Radical Prostatectomy Cohort

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• 作者：Michael H. Johnson^a ; Ashley E. Ross^a ; ^&lowast ; ; Mohammed Alshalalfa^b ; ^&lowast ; ; Nicholas Erho^b ; ^&lowast ; ; Kasra Yousefi^b ; ^&lowast ; ; Stephanie Glavaris^a ; Helen Fedor^a ; ^&lowast ; ; Misop Han^a ; ^&lowast ; ; Sheila F. Faraj^a ; ^&lowast ; ; Stephania M. Bezerra^a ; ^&lowast ; ; George Netto^a ; ^&lowast ; ; Alan W. Partin^a ; Bruce J. Trock^a ; ^&lowast ; ; Elai Davicioni^b ; Edward M. Schaeffer^c ; ^{eschaeffer@jhmi.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：prostatic neoplasms ; genomics ; prognosis ; neoplasm metastasis ; transcriptome
• 刊名：The Journal of Urology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：196
• 期：5
• 页码：1436-1444
• 全文大小：2907 K

文摘

Prostate cancer is clinically and molecularly heterogeneous. We determined the prognosis of men with ERG-ETS fusions and SPINK1 over expression.

Materials and Methods

Men were identified with intermediate or high risk localized prostate cancer treated with radical prostatectomy and no therapy before metastasis. A case-cohort design sampled a cohort (262) enriched with metastasis from the entire cohort and a cohort (213) enriched with metastasis from patients with biochemical recurrence. We analyzed transcriptomic profiles and subtyped tumors as m-ERG⁺, m-ETS⁺, m-SPINK1⁺ or Triple Negative (m-ERG^─/m-ETS^─/m-SPINK1^─), and multivariable logistic regression analyses, Kaplan-Meier and multivariable Cox models were used to evaluate subtypes as predictors of clinical outcomes.

Results

Overall 36%, 13%, 11% and 40% of prostate cancer was classified as m-ERG⁺, m-ETS⁺, m-SPINK1⁺ and Triple Negative, respectively. Univariable analysis demonstrated that m-SPINK1⁺ tumors were more common in African-American men (OR 5, 95% CI 1.6–16) but less commonly associated with positive surgical margins (OR 0.16, 95% CI 0.03–0.69) compared to the m-ERG⁺ group. Compared to the Triple Negative group, m-SPINK1⁺ showed similar associations with race and surgical margins in univariable and multivariable analyses across the entire cohort. Survival analyses did not show significant differences among m-ERG⁺, m-ETS⁺ and Triple Negative cases. m-SPINK1⁺ independently predicted prostate cancer specific mortality after metastasis (HR 2.48, 95% CI 0.96–6.4) and biochemical recurrence (HR 3, 95% CI 1.1–8).

Conclusions

SPINK1 over expression is associated with prostate cancer specific mortality in at risk men with biochemical and clinical recurrence after prostatectomy. ERG-ETS alterations are not prognostic for outcome.