Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Canada; Department of Laboratory Medicine, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
Department of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Clin Biochem. 2020 Jan;75:15-22. doi: 10.1016/j.clinbiochem.2019.10.002. Epub 2019 Oct 28.
Renal cell carcinoma (RCC) is often detected incidentally as a small renal mass (SRM; pT1a, ≤4 cm). It is clinically challenging to predict progression in patients with SRMs. This is largely due to the recent recognition of clinically progressive and non-progressive RCC-SRMs. It is critical to accurately stratify SRM patients according to risk to avoid unnecessary treatment. This is especially significant for elderly and infirm patients, where the risk of surgery outweighs mortality from SRMs.
We employed a qRT-PCR array-based approach and targeted qRT-PCR to identify and validate early, non-invasive diagnostic and prognostic biomarkers of RCC-SRMs. In total, we evaluated eighty urine samples, including 30 renal oncocytoma (≤4 cm) cases, 26 progressive and 24 non-progressive clear cell RCC-SRM (ccRCC-SRM) cases.
We identified nine urinary miRNAs which displayed significantly elevated expression in ccRCC-SRMs (pT1a; ≤4 cm) relative to renal oncocytoma (≤4 cm). Additionally, miR-328-3p displayed significantly down-regulated expression in progressive relative to non-progressive ccRCC-SRMs. Patients with elevated miR-328-3p expression had significantly longer overall survival (HR = 0.29, 95% CI = 0.08-1.03, p = 0.042) compared to patients with low miR-328-3p expression. We also found no significant association between miR-328-3p expression levels and gender, age, laterality, tumor size, or grade, suggesting that miR-328-3p is an independent prognostic biomarker.
Our in-depth miRNA profiling approach identified novel biomarkers for early-stage ccRCC-SRMs. Pretreatment characterization of urinary miRNAs may provide insight into early RCC progression and could potentially aid clinical decision-making, improving patient management and reducing overtreatment.
肾细胞癌 (RCC) 常作为小的肾肿块 (SRM;pT1a，≤4cm) 偶然发现。预测 SRM 患者的进展具有临床挑战性。这在很大程度上是由于最近认识到具有临床进展性和非进展性的 RCC-SRM。根据风险准确分层 SRM 患者以避免不必要的治疗至关重要。对于老年人和体弱者来说，这一点尤其重要，因为手术的风险大于 SRM 的死亡率。
我们采用基于 qRT-PCR 阵列的方法和靶向 qRT-PCR 来鉴定和验证 RCC-SRM 的早期、非侵入性诊断和预后生物标志物。我们总共评估了 80 个尿样，包括 30 个肾嗜酸细胞瘤（≤4cm）病例、26 个进展性和 24 个非进展性透明细胞肾细胞癌-SRM（ccRCC-SRM）病例。
我们发现 9 种尿 miRNA 在 ccRCC-SRM（pT1a；≤4cm）中表达显著升高，而在肾嗜酸细胞瘤（≤4cm）中表达显著降低。此外，miR-328-3p 在进展性 ccRCC-SRM 中表达显著下调，而在非进展性 ccRCC-SRM 中表达显著下调。miR-328-3p 表达升高的患者总生存期明显延长（HR=0.29，95%CI=0.08-1.03，p=0.042），而 miR-328-3p 表达较低的患者总生存期明显缩短。我们还发现 miR-328-3p 表达水平与性别、年龄、侧别、肿瘤大小或分级之间无显著相关性，提示 miR-328-3p 是一个独立的预后生物标志物。
我们深入的 miRNA 分析方法为早期 ccRCC-SRM 鉴定了新的生物标志物。尿 miRNA 的预处理特征可能有助于早期 RCC 进展，并可能有助于临床决策，改善患者管理，减少过度治疗。
