Xu Jinyuan, Lan Yujia, Yu Fulong, Zhu Shiwei, Ran Jianrong, Zhu Jiali, Zhang Hongyi, Li Lili, Cheng Shujun, Xiao Yun, Li Xia
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
Oncotarget. 2018 May 18;9(38):24936-24949. doi: 10.18632/oncotarget.25048.
Despite highly successful treatments for localized prostate cancer (PCa), prognostic biomarkers are needed to improve patient management and prognosis. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are key regulators with biological and clinical significance. By transcriptome analysis, we identified a set of consistently dysregulated lncRNAs in PCa across different datasets and revealed an eight-lncRNA signature that significantly associated with the biochemical recurrence (BCR)-free survival. Based on the signature, patients could be classified into high- and low-risk groups with significantly different survival (HR = 2.19; 95% CI = 1.67-2.88; < 0.0001). Validations in the validation cohorts and another independent cohort confirmed its prognostic value for recurrence prediction. Multivariable analysis showed that the signature was independent of common clinicopathological features and stratified analysis further revealed its role in elevating risk stratification of current prognostic models. Additionally, the eight-lncRNA signature was able to improve on the CAPRA-S score for the prediction of BCR as well as to reflect the metastatic potential of PCa. Functional characterization suggested that these lncRNAs which showed PCa-specific expression patterns may involve in critical processes in tumorigenesis. Overall, our results demonstrated potential application of lncRNAs as novel independent biomarkers. The eight-lncRNA signature may have clinical potential for facilitating further stratification of more aggressive patients who would benefit from adjuvant therapy.
尽管局部前列腺癌(PCa)的治疗取得了巨大成功,但仍需要预后生物标志物来改善患者管理和预后。越来越多的证据表明,长链非编码RNA(lncRNA)是具有生物学和临床意义的关键调节因子。通过转录组分析,我们在不同数据集中鉴定出一组在PCa中持续失调的lncRNA,并揭示了一种与无生化复发(BCR)生存期显著相关的8-lncRNA特征。基于该特征,患者可被分为高风险和低风险组,其生存期有显著差异(HR = 2.19;95% CI = 1.67 - 2.88;< 0.0001)。在验证队列和另一个独立队列中的验证证实了其对复发预测的预后价值。多变量分析表明,该特征独立于常见的临床病理特征,分层分析进一步揭示了其在提升当前预后模型风险分层中的作用。此外,8-lncRNA特征能够改善CAPRA-S评分对BCR的预测,并反映PCa的转移潜能。功能表征表明,这些表现出PCa特异性表达模式的lncRNA可能参与肿瘤发生的关键过程。总体而言,我们的结果证明了lncRNA作为新型独立生物标志物的潜在应用。8-lncRNA特征可能具有临床潜力,有助于对更多将从辅助治疗中获益的侵袭性更强的患者进行进一步分层。