Mehra Rohit, Shi Yang, Udager Aaron M, Prensner John R, Sahu Anirban, Iyer Matthew K, Siddiqui Javed, Cao Xuhong, Wei John, Jiang Hui, Feng Felix Y, Chinnaiyan Arul M
Department of Pathology, University of Michigan Health System, Ann Arbor, MI; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI; Michigan Center for Translational Pathology, Ann Arbor, MI.
Michigan Center for Translational Pathology, Ann Arbor, MI; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI.
Neoplasia. 2014 Dec;16(12):1121-7. doi: 10.1016/j.neo.2014.11.006.
Long noncoding RNAs (lncRNAs) are an emerging class of oncogenic molecules implicated in a diverse range of human malignancies. We recently identified SChLAP1 as a novel lncRNA that demonstrates outlier expression in a subset of prostate cancers, promotes tumor cell invasion and metastasis, and associates with lethal disease. Based on these findings, we sought to develop an RNA in situ hybridization (ISH) assay for SChLAP1 to 1) investigate the spectrum of SChLAP1 expression from benign prostatic tissue to metastatic castration-resistant prostate cancer and 2) to determine whether SChLAP1 expression by ISH is associated with outcome after radical prostatectomy in patients with clinically localized disease. The results from our current study demonstrate that SChLAP1 expression increases with prostate cancer progression, and high SChLAP1 expression by ISH is associated with poor outcome after radical prostatectomy in patients with clinically localized prostate cancer by both univariate (hazard ratio = 2.343, P = .005) and multivariate (hazard ratio = 1.99, P = .032) Cox regression analyses. This study highlights a potential clinical utility for SChLAP1 ISH as a novel tissue-based biomarker assay for outcome prognostication after radical prostatectomy.
长链非编码RNA(lncRNAs)是一类新出现的致癌分子,与多种人类恶性肿瘤有关。我们最近鉴定出SChLAP1是一种新型lncRNA,在一部分前列腺癌中表现出异常表达,促进肿瘤细胞侵袭和转移,并与致命性疾病相关。基于这些发现,我们试图开发一种针对SChLAP1的RNA原位杂交(ISH)检测方法,以1)研究从良性前列腺组织到转移性去势抵抗性前列腺癌的SChLAP1表达谱,以及2)确定ISH检测的SChLAP1表达是否与临床局限性疾病患者根治性前列腺切除术后的预后相关。我们当前研究的结果表明,SChLAP1表达随前列腺癌进展而增加,并且通过单因素(风险比=2.343,P=.005)和多因素(风险比=1.99,P=.032)Cox回归分析,ISH检测到的高SChLAP1表达与临床局限性前列腺癌患者根治性前列腺切除术后的不良预后相关。这项研究突出了SChLAP1 ISH作为一种新型基于组织的生物标志物检测方法在根治性前列腺切除术后预后预测中的潜在临床应用价值。