miR-210 as a Biomarker in Renal Carcinoma

Abstract

Renal cell carcinoma (RCC) is the most common urological neoplasm of the kidney in adults. The worldwide incidence and mortality rate is in the order of 270,000 cases and 120,000 deaths, respectively. Despite the fact that the diagnostic modalities and therapeutic techniques for RCC continue to improve, the overall incidence and mortality of RCC has increased in the last 20 years. The 5-year survival rate is approximately 98 % for stage I disease and approximately 50% for stage III or higher disease. These data underscore the importance of early detection and adequate prediction of prognosis of RCC.However, both early detection and adequate prediction are often difficult in the clinical setting. Renal tumor in the early stage is often asymptomatic and non-palpable, and it is impossible to correctly distinguish between RCC and BRT, even with the full use of diagnostic modalities such as imaging examinations, and determination of the adequate frequency of radiological imaging examinations as a screen for tumor recurrence is confusing. These problems are caused by the lack of an accurate biomarker for diagnosis and prognosis in RCC.Recent studies suggest that tissue microRNAs (miRNAs), which are non-protein-coding small RNAs, are involved in carcinogenesis and cancer progression. Further studies suggest that microRNAs are highly stable and abundant in the serum, urine, and other body fluids. Therefore, both tissue miRNAs and circulating miRNAs might be good biomarkers for diagnostic and prognostic considerations in a variety of cancers.Of all the miRNAs, miR-210, a well-known hypoxia-inducible miRNA, is one of the best studied miRNA in various cancers. Some research groups have reported that miR-210 was induced under hypoxic conditions via hypoxiainducible factors (HIFs) in various cancer cell lines. In the case of RCC, it is well known that HIF1 alpha and HIF2 alpha accumulate in clear cell carcinoma (ccRCC), which is the largest subtype of RCC, as a result of the deficiency of the von Hippel-Lindau (VHL) tumor suppressor gene. Therefore, a number of research groups have attempted to determine the relationship between miR-210 expression and the VHL-HIF pathway and to use miR-210 as a new biomarker in ccRCC.Regarding the possibility of using miR-210 as a diagnostic biomarker in RCC, two studies have reported that serum miR-210 expression was significantly higher in ccRCC patients than in healthy controls. These studies found no significant correlation between serum miR-210 levels and clinicopathological parameters of ccRCC patients. However, there has been no report regarding the utility of urine miR-210 as a diagnostic biomarker in RCC, and there has been no study of the difference between miR-210 expression levels of RCC and benign renal tumor.Regarding the use of miR-210 as a prognostic biomarker in RCC, some studies have demonstrated that high miR-210 expression in ccRCC tissue was statistically related to poor prognosis. On the other hand, several other studies have demonstrated precisely the opposite results regarding miR-210 levels and prognosis. Thus, there is no consensus regarding the utility of miR-210 as a prognostic biomarker. Further studies with a larger number of patients are warranted to validate these results.