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.
Highlights
Renal cell carcinoma (RCC) is the most common malignancy of the kidney, accounting for approximately 2% of global cancer diagnoses and deaths in 2020 [1, 2]
Our study has demonstrated that select Renal cell carcinomas (RCC)-related circRNAs can be detected in urine samples from clear cell RCC (ccRCC) patients, and their differential expression is associated with ccRCC status
This work highlights the diagnostic potential of circSOD2, circEGLN3 and linear EGLN3 for early detection of ccRCC
Summary
Renal cell carcinoma (RCC) is the most common malignancy of the kidney, accounting for approximately 2% of global cancer diagnoses and deaths in 2020 [1, 2]. Survival with RCC is dependent on clinical stage at first diagnosis, with 5-year survival rate around 90% for localized disease and 12% for metastatic disease [3]. 30% of ccRCC patients are first diagnosed with metastatic disease with poor overall prognosis and survival [7]. Identifying molecular markers in liquid biopsies (i.e. serum, urine) is a promising approach, which can potentially circumvent issues of tumor tissue heterogeneity and overcome limitations in tissue availability [10]. In this regard, non-invasive biomarkers that could be routinely used to screen for RCC at an early stage would be important for the clinical management of RCC
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