Novel lncRNA Signature (UFC1/PTENP1) as a Molecular Biomarker for the Diagnosis and Prognosis of Hepatocellular Carcinoma in an Egyptian Cohort

Long non-coding RNAs (lncRNAs) are key regulators of gene expression and play critical roles in cancer-related signaling networks. Dysregulation of antagonistic lncRNAs may contribute to hepatocarcinogenesis and disease progression. This study investigated the clinical significance and predictive value of two biologically antagonistic lncRNAs, UFC1 and PTENP1, as circulating biomarkers for hepatocellular carcinoma (HCC) in an Egyptian cohort. Expression levels of these lncRNAs were quantified in 100 HCC patients and 100 age- and sex-matched healthy controls. UFC1 was significantly upregulated (~2.9-fold), while PTENP1 was markedly downregulated (~4-fold) in HCC patients, with a strong inverse correlation (r = −0.609, p < 0.001). Both lncRNAs demonstrated higher diagnostic accuracy compared to alpha-fetoprotein (AFP); combining them with AFP further enhanced overall performance. UFC1 expression was increased progressively with advancing fibrosis grade and Barcelona Clinic Liver Cancer (BCLC) stage, while PTENP1 levels diminished with BCLC stage. Logistic regression confirmed UFC1 as an independent risk factor and PTENP1 as a protective factor for HCC. In conclusion, the blood-based UFC1/PTENP1 panel exhibits promising diagnostic accuracy and is associated with disease severity, surpassing AFP. Their fibrosis-associated dysregulation suggests a role in early hepatocarcinogenesis. This antagonistic lncRNA signature represents a potential, non-invasive tool for HCC detection and risk stratification, meriting further clinical validation.