Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer

被引:151
作者
Mehra, Rohit [1 ,2 ,3 ]
Udager, Aaron M. [1 ]
Ahearn, Thomas U. [4 ]
Cao, Xuhong [3 ]
Feng, Felix Y. [2 ,3 ,5 ]
Loda, Massimo [6 ]
Petimar, Joshua S. [4 ]
Kantoff, Philip [7 ]
Mucci, Lorelei A. [4 ]
Chinnaiyan, Arul M. [1 ,2 ,3 ,8 ]
机构
[1] Univ Michigan Hlth Syst, Dept Pathol, 2G332 UH,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA
[2] Univ Michigan Hlth Syst, Ctr Comprehens Canc, Ann Arbor, MI USA
[3] Michigan Ctr Translat Pathol, Ann Arbor, MI USA
[4] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
[5] Univ Michigan Hlth Syst, Dept Radiat Oncol, Ann Arbor, MI USA
[6] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA
[7] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[8] Howard Hughes Med Inst, Ann Arbor, MI USA
关键词
SChLAP1; Metastatic prostate cancer; long noncoding RNA; In situ hybridization; Lethal prostate cancer; RADICAL PROSTATECTOMY; PROGRESSION; COHORT;
D O I
10.1016/j.eururo.2015.12.003
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
100201 [内科学]; 100221 [泌尿外科学];
摘要
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. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:549 / 552
页数:4
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