MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis

Abstract

Background: Renal cell tumours (RCTs) are clinically, morphologically and genetically heterogeneous. Accurate identification of renal cell carcinomas (RCCs) and its discrimination from normal tissue and benign tumours is mandatory. We, thus, aimed to define a panel of microRNAs that might aid in the diagnostic workup of RCTs.

Methods: Fresh-frozen tissues from 120 RCTs (clear-cell RCC, papillary RCC, chromophobe RCC (chRCC) and oncocytomas: 30 cases each), 10 normal renal tissues and 60 cases of ex-vivo fine-needle aspiration biopsies from RCTs (15 of each subtype validation set) were collected. Expression levels of miR-21, miR-141, miR-155, miR-183 and miR-200b were assessed by quantitative reverse transcription-PCR. Receiver operator characteristic curves were constructed and the areas under the curve were calculated to assess diagnostic performance. Disease-specific survival curves and a Cox regression model comprising all significant variables were computed.

Results: Renal cell tumours displayed significantly lower expression levels of miR-21, miR-141 and miR-200b compared with that of normal tissues, and expression levels of all miRs differed significantly between malignant and benign RCTs. Expression analysis of miR-141 or miR-200b accurately distinguished RCTs from normal renal tissues, oncocytoma from RCC and chRCC from oncocytoma. The diagnostic performance was confirmed in the validation set. Interestingly, miR-21, miR-141 and miR-155 expression levels showed prognostic significance in a univariate analysis.

Conclusion: The miR-141 or miR-200b panel accurately distinguishes RCC from normal kidney and oncocytoma in tissue samples, discriminating from normal kidney and oncocytoma, whereas miR-21, miR-141 and miR-155 convey prognostic information. This approach is feasible in fine-needle aspiration biopsies and might provide an ancillary tool for routine diagnosis.

Figure 1

Distribution of miRNA expression levels in kidney tissues. (A) Normal vs tumour tissues. (B) Benign vs malignant tumour tissues. Statistically significant differences are represented as ***P<0.001, **P<0.01 and *P<0.02.

Figure 2

Distribution expression levels of (A) miR-21, (B) miR-141, (C) miR-155, (D) miR-183 and (E) miR-200b according with the histological subtype of RCTs. Statistically significant differences are represented as ***P<0.001, **P<0.003 and *P<0.0125.

Figure 3

ROC curves. ROC curves evaluating the performance of the gene panel (miR-141 and miR-200b) as a biomarker for malignant renal tumours (A and C) and as a biomarker of chRCC (B and D). (A and B) Performed in kidney tissue samples; (C and D) performed in ex-vivo aspiration renal biopsies.

Figure 4

Disease-specific survival according to pathological and molecular parameters. (A) Histopathological classification; (B) pathological stage; (C–E) miR expression levels.