Investigating Urinary Circular RNA Biomarkers for Improved Detection of Renal Cell Carcinoma

Abstract

Renal cell carcinomas (RCC) are usually asymptomatic until late stages, posing several challenges for early detection of malignant disease. Non-invasive liquid biopsy biomarkers are emerging as an important diagnostic tool which could aid with routine screening of RCCs. Circular RNAs (circRNAs) are novel non-coding RNAs that play diverse roles in carcinogenesis. They are promising biomarkers due to their stability and ease of detection in small quantities from non-invasive sources such as urine. In this study, we analyzed the expression of various circRNAs that were previously identified in RCC tumors (circEGLN3, circABCB10, circSOD2 and circACAD11) in urinary sediment samples from non-neoplastic controls, patients with benign renal tumors, and clear cell RCC (ccRCC) patients. We observed significantly reduced levels of circEGLN3 and circSOD2 in urine from ccRCC patients compared to healthy controls. We also assessed the linear variant of EGLN3 and found differential expression between patients with benign tumors compared to ccRCC patients. These findings highlight the potential of circRNA markers as non-invasive diagnostic tools to detect malignant RCC.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma

“…Among these, 54 studies were excluded due to the following reasons: non‐original articles ( n = 19), conference abstracts ( n = 3), and studies without available data for any of the defined outcomes ( n = 32). Ultimately, 41 studies consisting of 3485 patients with RCC were included in this study, among which 26 studies investigated clinicopathological features, 34,37–39,42–44,46–64 31 studies evaluated prognostic outcomes, 23,25,34–44,46,48,50,51,53–57,63–71 and eight studies assessed the diagnosis of RCC 34,40–42,48,58,72,73 . The studies were published between 2017 and 2022 and were conducted in China ( n = 38), Germany ( n = 2), and Canada ( n = 1).…”

“…The studies were published between 2017 and 2022 and were conducted in China ( n = 38), Germany ( n = 2), and Canada ( n = 1). The majority of studies utilized quantitative real‐time polymerase chain reaction (qRT‐PCR) on RCC tissue samples for their investigation (two studies evaluated serum samples, 58,72 and one study evaluated urine samples 73 ).…”

“…Ultimately, 41 studies consisting of 3485 patients with RCC were included in this study, among which 26 studies investigated clinicopathological features, 34,37-39,42-4 4,46-6 4 31 studies evaluated prognostic outcomes, 23,25,[34][35][36][37][38][39][40][41][42][43][44]46,48,50,51,[53][54][55][56][57][63][64][65][66][67][68][69][70][71] and eight studies assessed the diagnosis of RCC. 34,[40][41][42]48,58,72,73 The studies were published between 2017 and 2022 and were conducted in China (n = 38), Germany (n = 2), and Canada (n = 1). The majority of studies utilized quantitative real-time polymerase chain reaction (qRT-PCR) on RCC tissue samples for their investigation (two studies evaluated serum samples, 58,72 and one study evaluated urine samples 73 ).…”

Urine-based liquid biopsy: a new avenue for the management of renal cell cancer

“…Their expressions can be tissue-specific or cell-specific (10). The study by Peter et al investigated urinary cirRNA biomarkers for the detection of renal cell cancer (11). They observed significantly reduced levels of circEGLN3 and circSOD2 in urine from patients with a clear cell renal cell cancer when compared to healthy controls.…”

“…Previously, the circEGLN3 and circSOD2 biomarkers were shown to be upregulated in the tissues from renal cell cancer when compared to matched control tissues (12). It should be pointed out that urinary sediment was used in the study (11). Urinary sediment usually consists of exfoliated normal cells, tumor cells, immune cells, cellular debris and eventual bacteria.…”