Prognostic effect of a novel long noncoding RNA signature and comparison with clinical staging systems for patients with hepatitis B virus‐related hepatocellular carcinoma after hepatectomy

• Published in: Journal of digestive diseases 2020-11, Vol.21 (11), p.650-663
• Main Authors: Wu, Hao, Liu, Tian Tian, Feng, Yue Min, Xie, Xiao Yu, Su, Xiao Nan, Qi, Jian Ni, Zhu, Qiang, Qin, Cheng Yong
• Format: Article
• Language: English
• Subjects: Bioinformatics; clinical staging system; Fluorescence in situ hybridization; Gene expression; Genomes; Hepatectomy; Hepatitis; Hepatitis B; hepatitis B virus; Hepatocellular carcinoma; Liver cancer; long noncoding RNA; mRNA; Nomograms; Polymerase chain reaction; Survival; survival prediction
• ISSN: 1751-2972; 1751-2980
• DOI: 10.1111/1751-2980.12941

Objectives We aimed to establish a novel prognostic long noncoding RNA (lncRNA) signature for hepatitis B virus‐related hepatocellular carcinoma (HBV‐HCC) patients after hepatectomy and to validate its prognostic efficacy compared with other clinical staging systems. Methods Expression data of 374 HCC samples were retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression analyses were performed to develop the lncRNA model. The expression levels of lncRNAs were detected by qualitative real‐time polymerase chain reaction (qRT‐PCR) in HBV‐HCC. Then the qRT‐PCR‐based signature and nomogram were constructed and compared with those of other clinical staging systems in a clinical cohort and qRT‐PCR, RNA fluorescent in situ hybridization and comprehensive bioinformatics analyses were conducted. Results The signature containing five lncRNAs was constructed through TCGA. This model showed the highest predictive efficacy in patients with HBV‐HCC. Compared with normal liver tissues, all lncRNAs were highly expressed in HBV‐HCC. A four‐lncRNA signature containing LINC01116, DDX11‐AS1, LUCAT1 and FIRRE was developed based on the qRT‐PCR data in a clinical HBV‐HCC patient cohort. A Kaplan‐Meier analysis indicated that the low‐risk group had significantly longer overall survival than the high‐risk group. Additionally, the qRT‐PCR‐based four‐lncRNA formula was an independent prognostic factor and had better predictive efficacy for survival (area under the receiver operating characteristic curve 0.875) compared with other clinical staging systems in HBV‐HCC. The lncRNA‐mRNA co‐expression and enrichment analyses revealed the potential regulatory mechanisms of the lncRNA identified. Conclusion The four‐lncRNA model may be an effective prognostic signature and provides potential prognostic biomarkers and therapeutic targets for HBV‐HCC. We established a robust qualitative real‐time polymerase chain reaction‐based long noncoding RNA (lncRNA) signature for prognosis in patients with hepatitis B virus‐related hepatocellular carcinoma (HBV‐HCC) after hepatectomy, which is easy to apply and can guide effective clinical management in these patients. The model has better predictive efficacy for survival than other clinical staging systems (TNM, Child‐Pugh, Okuda, Barcelona‐Clinic Liver Cancer, the Chinese University Prognostic Index and the Cancer of Liver Italian Program). The lncRNA‐mRNA co‐expression network and enrichment analyses revealed the regulatory mechanisms o