The potential of CircRNA1002 as a biomarker in hepatitis B virus-related hepatocellular carcinoma.

Background: Although hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, there is a lack of effective diagnostic measures. Circular RNAs (circRNAs) can be used as biomarkers for monitoring the occurrence and development of HCC. However, a convenient and reliable serum circRNA biomarker is not currently available.

Materials & Methods: CircRNA expression profiles were explored using high-throughput sequencing technology, and targeted circRNAs and mRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). The biological functions of circRNAs were investigated using Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Downstream miRNAs and mRNAs of dysregulated circRNAs were predicted using TargetScan, miRanda, and miRDB; then circRNA-miRNA-mRNA interaction networks were constructed based on sequencing data and the Cancer Genome Atlas (TCGA).

Results: A total of 50,327 circRNAs were identified, with 1,187 circRNAs significantly differentially expressed between hepatitis B virus (HBV)-related HCC and HBV asymptomatic carriers. Among these circRNAs, four (circRNA1002, circRNA7941, circRNA 39338, and circRNA44142) were validated by RT-qPCR as being statistically different either in HCC tissue or serum samples. circRNA1002 was significantly down-regulated in both HCC serum and tissue, indicating its reliability. Bioinformatics analysis showed that circRNA1002-associated genes were enriched in GO terms relating to hormone pathway and cell-cell interaction processes, which are involved in the progression of HCC.

Conclusion: Our circRNA analysis of HCC patients and HBV asymptomatic carriers showed that circRNA1002 may be a reliable serum biomarker for HCC. These results could provide an improved assay for the early detection of HCC.