miQ—A novel microRNA based diagnostic and prognostic tool for prostate cancer

Abstract

Today, the majority of prostate tumors are detected at early stages with uncertain prognosis. Therefore, we set out to identify early predictive markers of prostate cancer with aggressive progression characteristics. We measured the expression of microRNAs (miRNA) using qRT-PCR in formalin fixed and paraffin embedded prostatic tissue samples from a Swedish cohort of 49 patients with prostate cancer and 25 without cancer and found seven of 13 preselected miRNAs to discriminate between the two groups. Subsequently, four discriminatory miRNAs were combined to a quota, denoted the miRNA index quote (miQ); ((miR-96-5p 3 miR-183-5p)/(miR-145-5p 3 miR221-5p)). The advantage of using a quote is increased discrimination, no need for house-keepings, and most important it may be an advantage considering the heterogeneity of the disease. miQ was found to successfully predict diagnosis (p < 0.0001) with high accuracy (area under the curve, AUC 5 0.931) that was verified in an independent Dutch cohort and three external cohorts, and significantly outperforming prostate-specific antigen. Importantly, miQ also has prognostic power to predict aggressiveness of tumors (AUC 5 0.895), metastatic statues (AUC 5 0.827) and overall survival (p 5 0.0013, Wilcoxon test HR 5 6.5, median survival 2 vs. 5 years), verified in the Dutch cohort. In this preliminary study, we propose that miQ has potential to be used as a clinical tool for prostate cancer diagnosis and as a prognostic marker of disease progression.Prostate cancer is the most prevalent cancer in the western world and the second leading cause of cancer death in men.

miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis

“…It is fundamental to increase the knowledge of how CRPC tumours progress so that patient morbidity can be reduced by newly developed therapies. In previous studies, we and others have observed downregulation of miR-145 in prostate cancer (9)(10)(11). Studying the correlation to clinical parameters in depth, we noted that miR-145 is associated with failure of androgen deprivation treatment, i.e.…”

“…The level of miR-145 have previously been found to be significantly decreased in prostate cancer specimens in our Swedish cohort (9). Here, the prognostic value of miR-145 expression levels, as measured by qRT-PCR, was investigated in the same cohort.…”

miR-183 in Prostate Cancer Cells Positively Regulates Synthesis and Serum Levels of Prostate-specific Antigen

“…miR-183 increases microRNA and protein levels of prostate-specific antigen Three miRNAs increasing PSA levels and predicted to target KLK3, miR-183 predicted to target the 3 0 UTR and upregulated in PCa patients [18], miR-650 predicted to target the CDS and promote tumourigenicity in gastric cancer [22], and miR-423 predicted to target the promoter and increase in metastatic breast cancer patients [23], were selected for further validation. Both secreted and intracellular levels of tPSA and fPSA were increased in PCa cells on transfection with mimic-miR-183, mimic-miR-423, and mimic-miR-650 compared with the scramble control ( Fig.…”

Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma

“…For example, the downregulation of miR-205 is useful in distinguished melanoma from nevus (Kozubek et al, 2013). Moreover, the relative expression of miR-205-5p in any Gleason pattern was decreased significantly compared with normal tissues (Tsuchiyama et al, 2013), to include prostate cancer samples compared with non-prostate cancer samples (Larne et al, 2013). These results could be explained by a previous report that miRNA expression profiles are tissue-specific (Lu et al, 2005).…”

“…While NPC miRNA expression studies have highlighted the importance and potential roles of miRNAs in disease, a deeper understanding is needed (Liu et al, 2013b). miR-183-5p was reported to be an early predictive biomarker for prostate cancer with aggressive progression characteristics (Larne et al, 2013), while conversely in lung cancer its expression was decreased . The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome ten) is known to be regulated by miR-183-5p (Sarver et al, 2010).…”