Identifying Prognostic Biomarkers and Key Pathways in Renal Clear Cell Carcinoma: A Pilot Study Using Integrated miRNA and Gene Expression Analysis

Background and Objective Renal clear cell carcinoma (RCCC) stands out as a prevalent and aggressive subtype of kidney cancer characterized by a challenging prognosis. The need to enhance patient outcomes in RCCC underscores the significance of identifying prognostic biomarkers and therapeutic targets. MicroRNAs (miRNAs) and the signaling pathways orchestrating RCCC pathogenesis emerge as promising candidates for such endeavors. Methods This study utilized publicly available gene expression data to compare miRNA profiles in nine RCCC and 11 normal kidney tissues. Rigorous bioinformatics analyses were employed to identify differentially expressed miRNAs and their associated gene targets. Prognostic significance was assessed, and a protein–protein interaction network was constructed to highlight pivotal RCCC hub genes. The expression and prognostic value of key hub genes and miRNAs were further validated in independent cohorts, including the GEO dataset GSE76351 and the TCGA–KIRC cohort via the Kaplan–Meier plotter. Expression of RUNX2 was confirmed using real‐time PCR in five cancer and five normal renal tissues. Results Fifteen DEMs were identified alongside 74 hub genes. The downregulation of miR‐26a‐1‐3p, miR‐144–3p, and miR‐144–5p was associated with a poorer prognosis in RCCC. The overexpression of CDK1 and RUNX2 was validated in an independent GEO dataset and correlated with decreased patient survival in the TCGA–KIRC cohort. Furthermore, a statistically significant but modest inverse association was observed between miR‐26a‐1‐3p and RUNX2 expression, indicating a possible miRNA–mRNA relationship. Significant enrichment was observed in pathways related to PI3K–Akt, MAPK, apoptosis, and cell cycle. The overexpression of RUNX2 was confirmed in our patient samples ( p value< 0.05). Conclusion This multistep validation study confirms that specific miRNAs and hub genes, particularly the miR‐26a‐1‐3p/RUNX2 axis, are potential prognostic indicators in RCCC. A comprehensive understanding of these biomarkers and their enriched signaling pathways provides deeper insight into the molecular underpinnings of RCCC, uncovering potential therapeutic opportunities.