Combination of MiR-378 and MiR-210 Serum Levels Enables Sensitive Detection of Renal Cell Carcinoma

Abstract

Serum microRNAs are emerging as a clinically useful tool for early and non-invasive detection of various cancer types including renal cell carcinoma (RCC). Based on our previous results, we performed the study to analyze circulating serum miR-378 and miR-210 in patients with various histological subtypes of RCC. RNA was purified from blood serum samples of 195 RCC patients and 100 healthy controls. The levels of miR-378 and miR-210 in serum were determined absolutely using quantitative real-time PCR. Pre- and postoperative levels of both microRNAs were compared in 20 RCC patients. Significantly increased serum levels of both miR-378 and miR-210 enabled to clearly distinguish RCC patients and healthy controls with 80% sensitivity and 78% specificity if analyzed in combination (p < 0.0001), and their levels significantly decreased in the time period of three months after radical nephrectomy (p < 0.0001). Increased level of miR-378 positively correlates with disease-free survival (p = 0.036) and clinical stage (p = 0.0476). The analysis of serum miR-378 and miR-210 proved their potential to serve as powerful non-invasive diagnostic and prognostic biomarkers in RCC.

The translational potential of microRNAs as biofluid markers of urological tumours

“…78 The use of more than one miRNA is generally recommended to obtain improved accuracy and robustness of results. 72 which is lower than the AUCs that had been reported in studies without independent study cohorts. 68,70,71 In two studies, a decline in the concentration of miR-210 and miR-378 was observed after nephrectomy for treatment of RCC 70,72 , and both miRNAs were suggested as potential indicators of cancer recurrence in follow-up monitoring of patients with RCC.…”

“…72 which is lower than the AUCs that had been reported in studies without independent study cohorts. 68,70,71 In two studies, a decline in the concentration of miR-210 and miR-378 was observed after nephrectomy for treatment of RCC 70,72 , and both miRNAs were suggested as potential indicators of cancer recurrence in follow-up monitoring of patients with RCC. Only one study demonstrated that miRNA expression could function as an independent prognostic marker, in which an increased expression level of miR-221 was associated with poor overall survival.…”

“…67,68,72,75 To date, no studies have been performed that investigate the clinical need for differentiating histological RCC subtypes from biofluid samples. Discrimination of RCC subtypes using miRNAs has already been achieved successfully using tissue samples and is important for the risk stratification of patients.…”

“…[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.…”