Diagnostic accuracy of circulating long noncoding RNAs in hepatocellular carcinoma: a systematic review and meta-analysis

BACKGROUND: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late diagnosis and the limited sensitivity of current screening biomarkers such as alpha-fetoprotein (AFP). Circulating long noncoding RNAs (lncRNAs) have recently emerged as promising, noninvasive biomarkers that may reflect the molecular mechanisms underlying hepatocarcinogenesis. This systematic review and meta-analysis aimed to comprehensively evaluate the diagnostic accuracy of circulating lncRNAs for detecting HCC. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Embase was performed up to March 2025 following the PRISMA-DTA guidelines. Eligible studies reporting the diagnostic performance of circulating lncRNAs for HCC were included. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model. Subgroup analyses were conducted according to sample type, detection method, and reference standard. RESULTS: Eighty-one studies encompassing over 6,000 participants were included. The pooled sensitivity and specificity of circulating lncRNAs were 0.83 (95% CI: 0.80-0.86) and 0.80 (95% CI: 0.75-0.84), respectively, with an area under the summary receiver operating characteristic (SROC) curve of 0.88. Serum-based assays showed slightly higher accuracy than plasma-based assays. lncRNAs also demonstrated good diagnostic performance in discriminating HCC from cirrhotic patients, as well as from patients with HBV-positive and HCV-positive status. CONCLUSION: Circulating lncRNAs exhibit high diagnostic accuracy and hold significant potential as complementary biomarkers to AFP for early HCC detection. Their mechanistic roles in tumor proliferation and immune regulation underscore their value in molecular diagnosis and personalized management of liver cancer.