Rohit Mehra1, Aaron M Udager2, Thomas U Ahearn3, Xuhong Cao4, Felix Y Feng5, Massimo Loda6, Joshua S Petimar3, Philip Kantoff7, Lorelei A Mucci3, Arul M Chinnaiyan8. 1. Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA. Electronic address: mrohit@med.umich.edu. 2. Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA. 3. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA. 4. Michigan Center for Translational Pathology, Ann Arbor, MI, USA. 5. Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI, USA. 6. Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. 7. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 8. Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA. Electronic address: arul@med.umich.edu.
Abstract
The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0-400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1-4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. PATIENT SUMMARY: We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.
The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0-400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1-4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. PATIENT SUMMARY: We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancerpatients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.
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