Combined identification of three lncRNAs in serum as effective diagnostic and prognostic biomarkers for hepatitis B virus‐related hepatocellular carcinoma

Abstract Hepatitis B virus‐related hepatocellular carcinoma (HBV‐related HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. This study aimed to identify the effective diagnostic and prognostic biomarkers for HBV‐related HCC. With HBV‐related HCC RNA‐sequencing data of The Cancer Genome Atlas (TCGA) database, 159 differentially expressed long noncoding RNAs (lncRNAs) between HBV‐related HCC and para‐carcinoma normal samples were identified, and 12 lncRNAs were eventually assessed for deeper research. Classification analysis developed a three‐lncRNA signature of AC005332.5, ELF3‐AS1 and LINC00665, which was demonstrated to be the most discriminatory with an AUC (Area under the curve) value of 0.913 (95% CI: 0.8610‐0.9665) and verified in validation patients. The expression levels of AC005332.5, ELF3‐AS1 and LINC00665 were significantly changed with different tumor stages or grades. Survival analysis revealed that AC005332.5, ELF3‐AS1 and LINC00665 were highly associated with the prognosis of overall survival. Additionally, the lncRNA signature yielded statistical significance to predict clinical outcomes independently from other clinical variables in validation patients, as suggested in the multivariate Cox hazards analysis. Conclusively, a three‐lncRNA signature of AC005332.5, ELF3‐AS1 and LINC00665 may serve as an excellent diagnostic biomarker for HBV‐related HCC and potential prognostic significance for HBV‐related HCC sufferers.