Expression Profile of Long Noncoding RNAs for Early Detection of Hepatocellular Carcinoma in Cirrhotic Patients

Abstract

Hepatocellular carcinoma is the most common primary liver cancer and one of the leading causes of cancer-related deaths worldwide. It develops mainly in patients with liver cirrhosis, a chronic condition marked by fibrosis, structural distortion, and nodular regeneration. Cirrhosis arises from long-term liver injury caused by hepatitis B and C infections, alcohol use, or aflatoxin exposure. These factors drive inflammation, oxidative stress, and DNA damage that promote malignant transformation of hepatocytes.In Egypt and many developing countries, hepatitis C infection remains the dominant cause of cirrhosis and hepatocellular carcinoma, creating a major health burden. Early detection of hepatocellular carcinoma is difficult because symptoms appear late and the available diagnostic tools are limited. Alpha-fetoprotein, the most used blood marker, lacks sensitivity and specificity, as it may stay normal in early stages or rise in benign liver diseases.New molecular approaches focus on long noncoding RNAs, which are RNA molecules longer than 200 nucleotides that do not code for proteins but regulate gene expression. These molecules influence cell growth, apoptosis, and tumor development. Several long noncoding RNAs, including HULC, HOTAIR, MALAT1, and PVT1, are involved in liver fibrosis and hepatocarcinogenesis by activating stellate cells, remodeling tissue, and promoting angiogenesis.Among them, PVT1 has shown strong association with tumor development and progression. It promotes cell proliferation, invasion, and survival through pathways such as Wnt/β-catenin, PI3K/AKT, and TGF-β. Its expression levels are higher in both liver tissue and blood of patients with hepatocellular carcinoma compared with cirrhotic or healthy individuals. High PVT1 levels also correlate with larger tumor size, advanced stage, and poor prognosis.These findings indicate that circulating long noncoding RNA PVT1 may serve as a sensitive and specific non-invasive biomarker for detecting hepatocellular carcinoma in cirrhotic patients, improving diagnostic accuracy beyond traditional markers like alpha-fetoprotein