## 6 miRNA Role in Clinical Practice and Future Perspective  
Despite the promising data, miRNAs' performance as diagnosis and prognosis markers remains unclear. Several studies have been published in the last few years regarding the utility of miRNAs in diagnosis and prognosis. Regarding diagnosis, [PERSON] et al. reported that miR-27, -28, -185, and let-7f-2 are overexpressed considerably in RCC specimens (\(p<0.05\)) in comparison to a healthy kidney [57]. [PERSON] et al. reported that 37 miRNAs were significantly under-expressed in conventional RCC, while the other 6 were overexpressed; miRNA 141 and miRNA-200 were especially down-regulated [58]. [PERSON] et al. also compared the expression of miRNA-15a in the urine of healthy renal parenchyma/benign tumors and RCC patients, and they found that it was upregulated in the second case (\(p<0.01\)) [59]. [PERSON] et al. explored the potential in diagnosis and prognosis of three miRNA signatures: miR-21, miR-584, and miR-155 [60]. They showed a sensitivity of 98.3% and a specificity of 97.2% of these miRNAs in discriminating RCC from normal controls. [PERSON] et al. reported that miRNA-1233 was increased in RCC patients, showing a sensitivity of 77.4% and specificity of 37.6%, as a diagnostic biomarker of RCC [61]. Regarding prognosis, [PERSON] et al. identified nine miRNAs that strongly correlated with RCC prognosis (\(p<0.01\)); in particular, they show high expression in patients with \begin{table}
\begin{tabular}{c c c c c c c} \hline
\begin{tabular}{c} High levels in \\ poor responder \\ patients to TKI \\ therapy \\ \end{tabular} \\ \hline \end{tabular}
\end{table} 
Table 1: _Cont._a poor prognosis [62]. [PERSON] et al. showed that miR-187 expression was downregulated in ccRCC specimens, decreased with advancing tumor grade and stage, and high levels correlated with survival after surgery [63]. The upregulation of miR-21 seems to be associated with the cancer-specific survival of ccRCC patients [64]. [PERSON] et al. showed that the ratio of miR-21 to miR-10B correlates independently with survival (\(p\) = 0.012) and the TNM stage [65]. [PERSON] et al. reported that in ccRCC patients, miR-21, miR-126, and miRNA-221 could independently predict cancer-related death [66]. [PERSON] et al. reported miRNA-125 as an independent adverse prognostic factor for recurrence and survival in RCC patients [67]. However, several investigations, including a higher number of patients, different stages and histologic subtypes or grades of differentiation of RCC, are required for the implementation of the current knowledge into clinical practice. After the discovery of miRNA, a high volume of reports outlined their various roles in tumor pathogenesis, clinical progression, and therapeutic management, according to the target gene. Although small renal masses are detected accidentally by abdominal imaging, a diagnosis of metastatic RCC occurs in about one-third of patients [68]; therefore, novel strategies to support early diagnosis are necessary. In this contest, miRNAs can be considered a valid option. According to [PERSON] et al., MiRNAs may be a diagnostic biomarker given their higher blood levels in RCC patients than in healthy volunteers; such levels were also shown to decrease during the postoperative period, therefore constituting a useful tool for monitoring therapeutic outcomes [69]. A renal cancer diagnosis is mainly confirmed through a computed tomography given its high sensitivity and specificity [45], although it determines exposure to ionizing radiations. Considering the lower incidence of RCC compared to colorectal or breast cancer, a screening program for the population is not provided by national healthcare systems, and miRNAs measurement for the prevention of RCC is not recommended. A future perspective may be represented by the assessment of the blood concentration of these biomarkers in patients with a greater diathesis to develop renal cancer.