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- Bjartell, Anders, et al.
(författare)
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Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:14, s. 4130-4138
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It has been suggested that cysteine-rich secretory protein 3 (CRISP-3) and p-microseminoprotein (MSP) are associated with outcome in prostate cancer. We investigated whether these markers are related to biochemical recurrence and whether addition of the markers improves prediction of recurring disease. Experimental Design: Tissue microarrays of radical prostatectomy specimens were analyzed for CRISP-3 and MSP by immunohistochemistry. Associations between marker positivity and postprostatectomy biochemical recurrence [prostate-specific antigen (PSA) > 0.2 ng/mL with a confirmatory level] were evaluated by univariate and multivariable Cox proportional hazards regression. Multivariable analyses controlled for preoperative PSA and pathologic stage and grade. Results: Among 945 patients, 224 had recurrence. Median follow-up for survivors was 6.0 years. Patients positive for CRISP-3 had smaller recurrence-free probabilities, whereas MSP-positive patients had larger recurrence-free probabilities. On univariate analysis, the hazard ratio for patients positive versus negative for CRISP-3 was 1.53 (P =0.010) and for MSP was 0.63 (P = 0.004). On multivariable analysis, both CRISP-3 (P = 0.007) and MSP (P = 0.002) were associated with recurrence. The hazard ratio among CRISP-3-positive/MSP-negative patients compared with CRISP-3-negative/MSP-positive patients was 2.38. Adding CRISP-3 to a base model that included PSA and pathologic stage and grade did not enhance the prediction of recurrence, but adding MSP increased the concordance index minimally from 0.778 to 0.781. Conclusion: We report evidence that CRISP-3 and MSP are independent predictors of recurrence after radical prostatectomy for localized prostate cancer. However, addition of the markers does not importantly improve the performance of existing predictive models. Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells.
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| 2. |
- Kamoun, Aurélie, et al.
(författare)
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A Consensus Molecular Classification of Muscle-invasive Bladder Cancer
- 2020
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 77:4, s. 420-433
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Tidskriftsartikel (refereegranskat)abstract
- Background: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, and participants: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts. Outcome measurements and statistical analysis: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models. Results and limitations: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment. Conclusions: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials. Patient summary: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.
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| 3. |
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| 4. |
- Tomlins, Scott A., et al.
(författare)
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The role of SPINK1 in ETS rearrangement-negative prostate cancers
- 2008
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Ingår i: Cancer Cell. - Amsterdam : Elsevier. - 1535-6108 .- 1878-3686. ; 13:6, s. 519-28
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Tidskriftsartikel (refereegranskat)abstract
- ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
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