Supplemental Digital Content is available in the text

Emerging studies have reported circRNAs were dysregulated in HCC. However, the clinical value of these circRNAs remains to be clarified. Herein, we aimed to comprehensively explore their association with the diagnosis, prognosis, and clinicopathological characteristics of HCC. PubMed, EMBASE, Web of Science, and Cochrane Library databases were comprehensively searched for eligible studies up to October 30, 2018. The diagnostic effect was evaluated by the pooled sensitivity, specificity, and other indexes. The pooled hazard ratio (HR) for overall survival (OS) and recurrence free survival (RFS) was calculated to assess the prognostic value. Ten studies on diagnosis, 12 on prognosis, and 23 on clinicopathology were identified from the databases. A total of 11 upregulated and 11 downregulated circRNAs showed an association with clinicopathological features of HCC. For the diagnosis analyses, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circRNAs for HCC were 0.74 (95%CI: 0.65-0.82) and 0.76 (95%CI: 0.70-0.81), 3.1 (95%CI: 2.5-3.8), 0.34 (95%CI: 0.25-0.47), and 9 (95%CI: 6-14), respectively. The area under SROC curve (AUC) was 0.81 (95% CI: 0.78–0.84), indicating moderate diagnostic accuracy. In stratified analyses, the diagnostic performance of circRNAs varied based on the source of control and specimen type. For the prognosis analyses, increased expression of upregulated circRNAs was associated with worse OS (HR: 3.67, 95%: 2.07-6.48), while high expression of downregulated circRNAs was associated with better OS (HR: 0.38, 95%: 0.30-0.48). In conclusion, this study reveals that circRNAs may serve as promising diagnostic and prognostic biomarkers for HCC. However, further investigations are still required to explore the clinical value of circRNAs.

Background Recent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear. Methods The plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines. Results Among candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines. Conclusions AP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.

Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through‐put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT‐PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa‐miR‐486‐5p, ‐25‐3p, and ‐92a‐3p and ‐1‐3p was further validated by qRT‐PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.