This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up.
In conclusion, Serum exosomal miR-210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.
We identified and validated multiple miRNAs dysregulated in ccRCC tissues; miR-155-5p and miR-210-3p were predictive of ccRCC recurrence, pointing to potential utility as biomarkers and underlying biological mechanisms.
A total of 7 publicly available and independent RCC miRNA expression profiling datasets were collected, and 2 upregulated (hsa-miR-155-5p and hsa-miR-210-5p) and 6 downregulated (hsa-miR-138-5p, hsa-miR-141-5p, hsa-miR-200c-5p, hsa-miR-362-5p, hsa-miR-363-5p and hsa-miR-429) meta-signature miRNAs in renal carcinoma were identified.
In this study, a new nanopore-based detection scheme utilizing a borosilicate micropipette and an assay of complementary γ-peptide nucleic acid (γ-PNA) probes conjugated to polystyrene beads have been reported for the detection of miR-204 and miR-210 related to the clear cell Renal Cell Carcinoma (ccRCC).
To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis.
In a cohort of 45 patients, the high expression of miR-21 (HR: 5.46, 95%CI: 2.02-53.39) and miR-210 (HR: 6.85, 95%CI: 2.13-43.36), the low expression of miR-141 (HR: 0.16, 95%CI: 0.004-0.18), miR-200c (HR: 0.08, 95%CI: 0.01-0.43) and miR-429 (HR: 0.18, 95%CI: 0.02-0.50) were associated with poor cancer-specific survival (CSS) following RCC resection.
A number of predicted targets that might be involved in carcinogenesis and aggressive tumor behavior were identified. miR-210 is a potential therapeutic target and independent marker of poor prognosis of ccRCC.
Further, many studies using miRNA microarray analysis demonstrated that miR-210 expression in clear cell carcinoma (CCC), which is the largest subtype of RCC, was significantly upregulated in tumor tissue.
In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study.
Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue.