Khella Heba W Z, Daniel Nicole, Youssef Leza, Scorilas Andreas, Nofech-Mozes Roy, Mirham Lorna, Krylov Sergey N, Liandeau Evi, Krizova Adriana, Finelli Antonio, Cheng Yufeng, Yousef George M
Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
J Clin Pathol. 2017 Oct;70(10):854-859. doi: 10.1136/jclinpath-2017-204341. Epub 2017 Mar 30.
Clear cell renal cell carcinoma (ccRCC) is the most common adult kidney cancer. It is an aggressive tumour with unpredictable outcome. The currently used clinical parameters are not always accurate for predicting disease behaviour. miR-10b is dysregulated in different malignancies including RCC.
We assessed the clinical utility of miR-10b as a prognostic marker in 250 patients with primary ccRCC. We examined the correlation between miR-10b and clinicopathological parameters. We compared miR-10b expression among different RCC subtypes and normal kidney tissue.
We observed a stepwise decrease of miR-10b expression from normal kidney to primary ccRCC and a further decrease from primary to metastatic RCC. miR-10b expression was significantly lower in stages III/IV compared with stages I/II (p=0.038). Using a binary cut-off, miR-10b-positive patients had significantly longer disease-free survival (HR=0.47, CI 0.28 to 0.79, p=0.004). In the subgroup of patients with tumour size >4 cm, higher miR-10b expression was associated with significant longer disease-free and overall survival (p=0.001 and p=0.036, respectively). miR-10b was significantly downregulated in ccRCC compared with normal kidney (p<0.0001), and oncocytoma (p=0.031). It was also downregulated in chromophobe RCC. In addition, we identified a number of miR-10b-predicted targets and pathways that are involved in tumourigenesis.
Our data point to miR-10b as a promising prognostic marker in ccRCC with potential therapeutic applications.
透明细胞肾细胞癌（ccRCC）是最常见的成人肾癌。它是一种侵袭性肿瘤，预后不可预测。目前使用的临床参数在预测疾病行为方面并不总是准确的。miR-10b在包括肾癌在内的不同恶性肿瘤中表达失调。
我们评估了miR-10b作为250例原发性ccRCC患者预后标志物的临床效用。我们研究了miR-10b与临床病理参数之间的相关性。我们比较了不同肾癌亚型和正常肾组织中miR-10b的表达。
我们观察到从正常肾脏到原发性ccRCC，miR-10b表达呈逐步下降，从原发性到转移性ccRCC进一步下降。与I/II期相比，III/IV期miR-10b表达显著降低（p=0.038）。采用二元临界值，miR-10b阳性患者的无病生存期显著更长（HR=0.47，CI 0.28至0.79，p=0.004）。在肿瘤大小>4 cm的患者亚组中，较高的miR-10b表达与显著更长的无病生存期和总生存期相关（分别为p=0.001和p=0.036）。与正常肾脏（p<0.0001）和嗜酸细胞瘤（p=0.031）相比，ccRCC中miR-10b显著下调。在嫌色性肾癌中也下调。此外，我们鉴定了一些参与肿瘤发生的miR-10b预测靶点和通路。
我们的数据表明miR-10b是ccRCC中有前景的预后标志物，具有潜在的治疗应用价值。
