Kowalik Casey G, Palmer Drew A, Sullivan Travis B, Teebagy Patrick A, Dugan John M, Libertino John A, Burks Eric J, Canes David, Rieger-Christ Kimberly M
Department of Urology, Lahey Hospital and Medical Center, Burlington, MA, USA.
Department of Translational Research - Ian C. Summerhayes Cell and Molecular Biology Laboratory, Lahey Hospital and Medical Center, Burlington, MA, USA.
BJU Int. 2017 Sep;120(3):428-440. doi: 10.1111/bju.13886. Epub 2017 May 18.
To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue.
RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan-Meier and Cox proportional hazards analyses.
Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS.
This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.
确定转移性透明细胞肾细胞癌（ccRCC）的微小RNA（miRNA）特征以及肾切除术和活检标本中提示癌症特异性生存（CSS）的特征。我们还试图确定一个miRNA组合能否区分ccRCC组织和良性组织。
从肾切除术和肾活检标本中分离RNA（分别为n = 156和n = 46）。样本分组为：良性、非进展性和进展性ccRCC。通过微阵列分析miRNA，并通过定量逆转录-聚合酶链反应进行验证。开发生物标志物特征以预测肾切除术和活检标本中的癌症状态。使用Kaplan-Meier和Cox比例风险分析来检查CSS。
微阵列分析显示，比较非进展性肿瘤和进展性肿瘤时，有20种miRNA差异表达。在肾切除标本中验证的生物标志物特征区分良性和ccRCC标本的灵敏度为86.7%，特异性为92.9%。另一个特征区分非进展性和进展性ccRCC的灵敏度为93.8%，特异性为83.3%。这些生物标志物也能区分活检标本中的癌症状态。miR-10a-5p、-10b-5p和-223-3p的水平与CSS相关。
本研究确定了ccRCC样本中差异表达的miRNA，以及与CSS相关的miRNA。本研究中鉴定的生物标志物有可能识别出可能患有进展性ccRCC的患者，尽管这些结果尚属初步，但可能有助于根据活检标本区分侵袭性和惰性ccRCC。
