Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer

Abstract

In addition to their potential as tissue-based markers for cancer classification and prognostication, the study of microRNAs (miRNAs) in blood circulation is also of interest. In the present study, we investigated the amounts of three cancer-related miRNAs, miR-21, -141, and -221 in blood plasma of prostate cancer (PCa) patients. A cohort of 51 patients with PCa was enrolled into the study, and miRNAs were measured in two subgroups, with localized/local advanced or metastatic PCa. A group of 20 healthy individuals served as the control group. miRNAs were quantified from the total RNA fraction using 200 μl plasma and the small RNA molecule RNU1A as a control for normalizing the miRNA amounts in circulation. We found similar levels of three miRNAs in healthy subjects with median values of 0.039, 0.033 and 0.04, respectively; (p = n.s.). In the patients, the miRNA levels were higher, with miR-21 being the highest (median, 1.51). The miR-221 levels were intermediate (median, 0.71) while the miR-141 displayed the lowest levels (median, 0.051). The differences between the control group and the patients were highly significant for the miR-21 (p < 0.001; area under the curve (AUC), 88%) and -221 (p < 0.001; AUC, 83%) but not for the miR-141 (p = 0.2). In patients diagnosed with metastatic PCa, levels of all three miRNAs were significantly higher than in patients with localized/local advanced disease where the difference for the miR-141 was most pronounced (p< 0.001; AUC, 75.5%). In conclusion, analysis of miR-21, -141, and -221 in blood of PCa patients reveals varying patterns of these molecules in clinical subgroups of PCa.

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

“…14 Mitchell et al 8 were the first to describe the overexpression of circulating miR-141 in advanced PCa, and Bryant et al 15 discovered an association of miR-141 with metastatic PCa. In addition, Yaman Agaoglu et al 16 Figure 1 Box plot of different serum miR-141 expression levels in different groups of patients (group 1, BPH patients, n56; group 2, LPC patients, n520; group 3, HNPC patients, n510; group 4, HSPC patients, n510; group 5, HRPC patients, n510). By one-way ANOVA test and independent samples t-test, serum miR-141 expressed higher in the patients with bone metastasis (HNPC, HSPC and HRPC patients) than those in BPH and LPC patients (P,0.001).…”

The translational potential of microRNAs as biofluid markers of urological tumours

“…121,126 In nine out of these 15 miR-141-studies, miR-141 was only evaluated as a marker of advanced or metastatic prostate cancer (Table 3). 20,84,96,99,101,103,[113][114][115] but was frequently, if at all reported, not better than the routine marker PSA. 114,115,118 These data underline the fact that the clinical relevance of a marker can only be truly assessed if studies with similar questions are compared: a useful diagnostic marker might be a useless prognostic marker and vice versa.…”

Circulating microRNAs: macro-utility as markers of prostate cancer?

“…In a study aimed at testing the diagnostic utility of three specific PCa-associated miRNAs, miR-21, miR-141, and miR-221, Yaman Agaoglu et al (2011) found that miR-21 and miR-221 were elevated in the plasma of men with localized cancer compared with healthy controls. Moreover, these three miRNAs were increased in samples from men with bone metastases compared with men with localized/locally advanced disease, and miR-141 could accurately distinguish between these groups (AUCZ0.755).…”

“…Like miR-375, miR-141 is elevated in both the circulation of men with PCa and prostate tumors (Mitchell et al 2008, Brase et al 2011, Gonzales et al 2011, Selth et al 2011, Yaman Agaoglu et al 2011, Bryant et al 2012. miR-141 is a member of the miR-200 family, which functions to repress the epithelial to mesenchymal transition (EMT) by targeting the ZEB family of transcription factors (Bracken et al 2009).…”