Objective : The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients. Methods : All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators. Results : In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [ EZH2 ], kinesin family member 23 [ KIF23 ], chromobox 2 [ CBX2 ], centrosomal protein 55 [ CEP55 ], cell division cycle 25A [ CDC25A ], and claspin [ CLSPN ]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P <0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation. Conclusions : Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.

The present study aimed to investigate the clinical significance and prospective molecular mechanism of cystatin (CST) genes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The role of CST genes in the molecular mechanism of HCC was revealed through bioinformatics analysis. The clinical significance of CST genes was investigated using GSE14520-derived data from patients with HBV-related HCC. Gene set enrichment analysis (GSEA) was used to identify pathways in which the CST genes were enriched, as well as the association between these pathways and HCC. The expression levels of CST1, CST2, CST5, CSTA and CSTB genes were higher in HCC tissue compared with in normal tissue; conversely, CST3 and CST7 were reduced in HCC tissue. Subsequent receiver operating characteristic analysis of the CST genes demonstrated that CST7 and CSTB genes may function as potential diagnostic markers for HCC. Furthermore, the expression levels of CST6 and CST7 were strongly associated with recurrence-free survival and overall survival of patients with HBV-related HCC. GSEA of the CST genes revealed that CST7 was significantly enriched in tumor evasion and tolerogenicity, cancer progenitors, liver cancer late recurrence, liver cancer progression and several liver cancer subclasses. In addition, CST genes demonstrated homology in terms of protein structure and were revealed to be strongly co-expressed. The present findings suggested that CST7 and CSTB genes may serve as potential prognostic and diagnostic biomarkers for HCC.

The present study aimed to determine the clinical significance and potential molecular mechanisms of CC motif chemokine receptor (CCR) genes in patients with early-stage pancreatic ductal adenocarcinoma (PDAC). The transcriptomic, survival and clinical data of 112 patients with early-stage PDAC who underwent pancreaticoduodenectomy were obtained from The Cancer Genome Atlas. The prognostic values of the CCR genes involved in early-stage PDAC were evaluated using Kaplan-Meier analysis and the multivariate Cox proportional risk regression model, and the potential molecular mechanisms were determined using bioinformatics tools. The identified CCRs closely interacted with each other at both the gene and protein levels. High expression levels of CCR5 [adjusted P=0.012; adjusted hazard ration (HR)=0.478, 95% confidence interval (CI)= 0.269-0.852], CCR6 (adjusted P= 0.026; adjusted HR= 0.527, 95% CI= 0.299-0.927) and CCR9 (adjusted P=0.001; adjusted HR=0.374, 95% CI= 0.209-0.670) were significantly associated with longer overall survival times in patients with early-stage PDAC. The contribution of CCR5, CCR6 and CCR9 to the outcome of early-stage PDAC was also demonstrated. Combined survival analysis of CCR5, CCR6 and CCR9 suggested that patients with high expression levels of these CCRs exhibited the most favorable outcomes. A prognostic signature was constructed in terms of the expression level of CC5, CCR6 and CCR9, and time-dependent receiver operating characteristic curves indicated that this signature was able to effectively predict the outcome of patients with early-stage PDAC. The potential molecular mechanisms of CCR5, CC6 and CCR9 in PDAC include its intersection of the P53, nuclear factor (NF)-κB, generic transcription, mitogen-activated protein kinase and STAT signaling pathways. Collectively, this highlights that CCR5, CCR6 and CCR9 are potential prognostic biomarkers for early-stage PDAC.