Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, constituting 70-80% of all renal malignancies [1]. Today, the diagnosis and prognosis of ccRCC rely heavily on tissue biopsy, an invasive procedure that may endanger patients and is limited in its ability to capture the heterogeneity of the tumor. Moreover, tissue biopsies are often performed only after the disease has progressed to an advanced stage, limiting opportunities for early intervention [2]. In contrast, using liquid biopsy – blood plasma, urine, or other biofluids – provides a minimally invasive, repeatable alternative that provides real-time insights into tumor dynamics. Tumor-derived biomarkers detectable in plasma, such as circulating DNA, RNA, or proteins, become powerful tools in this context [3].
The WNT and MYC pathways are important in tumorigenesis because they regulate essential cellular processes that are often dysregulated in cancer. The WNT pathway key gene is CTNNB1 and C-MYC is the main gene in MYC. This C-MYC and CTNNB1 are of particular interest due to their known roles in cell proliferation, metabolic reprogramming, and tumor progression in ccRCC [4][5].
The use of liquid biopsy-based methodologies for detecting ccRCC could revolutionize diagnostic protocols by providing a rapid and cost-efficient way of identifying malignant renal tumors. This study investigates the potential of C-MYC and CTNNB1 as non-invasive biomarkers for the diagnosis of ccRCC.
In this study, RNA was isolated from 53 ccRCC patients and 26 individuals with benign renal tumors, of which 8 were angiomyolipomas and 18 were oncocytomas. Quantitative reverse transcription PCR (RT-qPCR) method was used for the analysis. ROC analysis was used to determine the diagnostic potential of the C-MYC and CTNNB1 genes, with GAPDH serving as the reference gene.
The results’ analysis demonstrated differential expression of the C-MYC and CTNNB1 genes in ccRCC cases compared to control samples. Both CTNNB1 and C-MYC effectively distinguished ccRCC cases from angiomyolipomas, with an AUC of 0.69. However, their ability to distinguish ccRCC from oncocytomas was lower, with CTNNB1 achieving an AUC = 0.58 and C-MYC an AUC = 0.54. Furthermore, CTNNB1 expression correlated with tumor diameter in the ccRCC patient group.
Changes in C-MYC and CTNNB1 gene expressions detected in blood plasma samples may be useful for the early detection and prognosis of ccRCC. However, additional investigations are required to validate CTNNB1 and C-MYC as reliable non-invasive biomarkers for ccRCC.