Elevated CircYthdc2 expression is correlated with aggressive features and poor progression-free survival in hepatocellular carcinoma.

Objective: Liver hepatocellular carcinoma (LIHC) is a major contributor to cancer-related mortality. While early detection is crucial for improving outcomes, current diagnostic methods lack optimal sensitivity and specificity. Circular RNAs (circRNAs) have emerged as promising biomarkers due to their stability and tissue-specific expression.

Methods: Bioinformatic analysis was performed using UALCAN database to examine YTHDC2 methylation and expression patterns. Tissue and serum samples were collected from 72 LIHC patients and matched controls. CircYTHDC2 expression was assessed in tissues, serum, and cell lines via qRT-PCR. CircYTHDC2's diagnostic potential was evaluated through ROC analysis and stability testing. Associations between circYTHDC2 levels, clinicopathological features, and survival were analyzed.

Results: Bioinformatic analysis revealed reduced YTHDC2 promoter methylation and elevated expression in LIHC tissues. CircYTHDC2 showed significant upregulation in LIHC tissues, serum, and cell lines compared to controls. ROC analysis demonstrated high diagnostic accuracy for circYTHDC2 in tissues (AUC = 0.846) and serum (AUC = 0.788). CircYTHDC2 exhibited remarkable stability against RNase degradation. Elevated circYTHDC2 levels significantly correlated with advanced BCLC stage, larger tumor size, intrahepatic metastasis, and portal invasion. High circYTHDC2 expression was associated with shorter progression-free survival (P = 0.025). Additionally, we found circYTHDC2 bound to YTHDC2 and was positively regulated by YTHDC2 in an m6A-dependent manner.

Conclusion: CircYTHDC2 represents a stable, clinically viable biomarker for LIHC, demonstrating significant diagnostic accuracy and prognostic value. Its strong correlation with aggressive tumor features and survival outcomes suggests potential utility in clinical management of LIHC patients.