MicroRNAs as Urinary Biomarker for Oncocytoma

Abstract

The identification of benign renal oncocytoma, its differentiation from malignant renal tumors, and their eosinophilic variants are a continuous challenge, influencing preoperative planning and being an unnecessary stress factor for patients. Regressive changes enhance the diagnostic dilemma, making evaluations by frozen sections or by immunohistology (on biopsies) unreliable. MicroRNAs (miRs) have been proposed as novel biomarkers to differentiate renal tumor subtypes. However, their value as a diagnostic biomarker of oncocytoma in urines based on mechanisms known in oncocytomas has not been exploited. We used urines from patients with renal tumors (oncocytoma, renal cell carcinoma: clear cell, papillary, chromophobe) and with other urogenital lesions. miRs were extracted and detected via qRT-PCR, the respective tumors analyzed by immunohistology. We found isocitrate dehydrogenase 2 upregulated in oncocytoma and oncocytic chromophobe carcinoma, indicating an increased Krebs cycle metabolism. Since we had shown that all renal tumors are stimulated by endothelin-1, we analyzed miRs preidentified by microarray after endothelin-1 stimulation of renal epithelial cells. Four miRs are proposed as presurgical urinary biomarkers due to their known regulatory mechanism in oncocytoma: miR-498 (formation of the oncocytoma-specific slice-form of vimentin, Vim3), miR-183 (associated with increased CO2 levels), miR-205, and miR-31 (signaling through downregulation of PKC epsilon, shown previously).

miRNA-based biomarkers, therapies, and resistance in Cancer

“…Another group identified the DNA methylation of genomic loci encoding miRNAs (mgmiRs) in vitro cell lines, and successfully developed a seven-mgmiR diagnostic panel for HNSCC [127]. A more instance, four miRNAs (miR-498, miR-183, miR-205, and miR-31), which are suitable indicators in urine for the presurgical identification of representative benign renal oncocytoma, can well conduct preoperative plans and avoid some unnecessary stress for patients [135]. These miRNA panels may be more effective than sole miRNA used, but, both with outstanding significance for cancer patients.…”

Diagnostic Performance of Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of Solid Renal Masses

“…Therefore, it seems desirable to allow for non-invasive diagnosis of oncocytoma or angiomyolipoma. The use of biomarkers, such as microRNAs, offers a promising approach for non-invasive characterization of unclear renal masses [ 27 , 28 ]. Further studies with a focus on the diagnostic accuracy of these biomarkers are needed in the future.…”

Analysis of expression, epigenetic, and genetic changes of HNF1B in 130 kidney tumours

“…RO is the second most frequent benign renal tumour of the renal parenchyma and represents 3–7% of all renal lesions 47 . Among others, morphologically it is characterised by eosinophilic features, which may resemble the eosinophilic subtype of chRCC and the distinction between these two entities can represent a diagnostic challenge 48 . Given that these are tumours with crucially different biological behaviours, proper diagnosis is key for correct postoperative surveillance and for the prognosis of the patient.…”