A panel of five serum miRNAs as a potential diagnostic tool for early-stage renal cell carcinoma

Abstract

Circulating microRNAs (miRNAs) are emerging as clinically useful tools for cancer detection; however, little is known about their early diagnostic impact on RCC. The levels of 754 serum miRNAs were initially determined using a TaqMan Low Density Array in two pooled samples from 25 RCC and 25 noncancer controls. Markedly dysregulated miRNAs in RCC cases were subsequently validated individually by qRT-PCR in another 107 patients and 107 controls arranged in two sets. The serum levels of miR-193a-3p, miR-362 and miR-572 were significantly increased whereas the levels of miR-28-5p and miR-378 were markedly decreased in patients with RCC, even in those with stage I disease, compared with the noncancer controls (P < 0.01). The areas under the ROC curve (AUCs) for the 5 combined miRNAs were 0.807 (95% CI, 0.687–0.928) and 0.796 (95% CI, 0.724–0.867) for the training set and the validation set, respectively. Furthermore, the panel enabled the differentiation of stage I RCC from controls with AUC of 0.807 (95% CI, 0.731–0.871), a sensitivity of 80% and a specificity of 71%. This panel of 5 serum miRNA may have the potential to be used clinically as an auxiliary diagnostic tool for the early detection of RCC.

miR-144-3p as a novel plasma diagnostic biomarker for clear cell renal cell carcinoma

“…It has been clearly demonstrated that miRNAs steadily existed in plasma [8] and the regulation of circulating miRNAs was closely associated with cancer types and disease progression [9,10]. In RCC diagnosis, it has been previously found that miR-210, miR-378, miR-451, miR-193a-3p, miR-362, miR-572, miR-28-5p, and miR-378 [11][12][13][14] all had the potential to be the plasma or serum biomarker for RCC. However, these biomarkers lack a high accuracy in RCC diagnosis with single detection and it is necessary to combine 2 or more members to improve the diagnostic accuracy, which would significantly increase the testing costs in clinical practice.…”

The epigenetic landscape of renal cancer

“…The heterogeneity of mutations within tumours, which results in different subclones that evolve differently, is a major obstacle to clinical translation 235,236,238,239 . Intratumour heterogeneity of DNA methylation might, however, not be as pronounced as intratumour heterogeneity of genomic changes.…”

The translational potential of microRNAs as biofluid markers of urological tumours

“…[65][66][67][68][69][70][71][72][73][74][75][76] Specifically, relatively few studies, including only one multicentre study 67 , have been conducted, and most studies did not perform an internal validation with a training and validation set or even an internal validation approach, such as bootstrapping or cross-validation. Moreover, all studies except one used serum as the source of RNA despite plasma being the blood component of choice since the release of miRNAs from blood cells such as the miRNA-enriched platelets into serum occurs during the coagulation process.…”

“…In addition, different strategies were applied for normalizing RT-qPCR data and contrasting results regarding the regulation of miR-378, as example, were reported already in three studies. 68,72,74 All studies conducted to date were primarily focused on the diagnostic objective of discrimination between patients with RCC and healthy control subjects.…”

“…The study cohorts consisted either of patients with only clear cell RCC (ccRCC) [69][70][71]74 -the subtype with the highest incidence -or combined with patients of papillary, chromophobe or sarcomatoid RCC. 67,68,72,75 To date, no studies have been performed that investigate the clinical need for differentiating histological RCC subtypes from biofluid samples.…”