Background & Aims: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. Methods: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted.

Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PP-P2CA may be involved in HCC were determined using miR-Walk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PP-P2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

Background: To investigate the role of the PPP2CA gene in the prognosis of patients with hepatocellular carcinoma (HCC) and its molecular biological characteristics. Methods: We performed comparison of the expression of PPP2CA in HCC and non-HCC tissues of HCC patients who underwent surgery for the first time in the Tumor Hospital of Guangxi Medical University from July 2017 to July 2019, and retrospectively analyzed the relevant clinical data and prognosis. The GSE76427 data set and bioinformatics and public databases were used to compare the expression of PPP2CA between HCC and non-cancer tissues. Gene Ontology (GO) analysis was performed of PPP2CA and its differential genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A protein-protein interaction (PPI) network of PPP2CA and its differentially expressed genes (DEGs) was constructed from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape software. Results: The immunohistochemistry (IHC) of tissue sections confirmed that PPP2CA was highly expressed in most HCC tissues; the high expression of PPP2CA was significantly correlated with microvascular invasion (MVI) and portal vein tumor thrombi (P<0.05). Participants in the PPP2CA high expression group had worse overall survival (OS; P=0.04) and recurrence-free survival (RFS; P=0.019). The PPP2CA gene and 71 DEGs were mainly enriched in the nuclear division, organelle fission, nuclear chromosome separation, and chromatid separation process, and KEGG analysis revealed enrichment in drug metabolism-cytochrome metabolism of xenobiotics by P450 and cytochrome P450. Finally, through the PPI network, CCNA2, AURKB, TOP2A, NCAPG, MCM2, CDC20, CCMB2, AURKA, and MGST1 were identified as the top 9 highly connected hub genes. Conclusions:The PPP2CA gene is highly expressed in HCC tissues. The high expression of PPP2CA is significantly associated with poor prognosis. Through the analysis of DEGs, GO and KEGG pathway analysis, it was found that PPP2CA may act on liver cancer through multiple targets and multiple pathways, and PPP2CA plays a promoting role in HCC.

The study aimed to investigate the ability of inflammation-immunity-nutrition score (IINS) and inflammatory burden index (IBI), individually or in combination, to predict prognosis of hepatocellular carcinoma (HCC) patients after hepatectomy. Methods: A total of 701 patients who underwent HCC resection at Guangxi Medical University Cancer Hospital were enrolled in the study. An IINS ranging from 0 to 3 was defined based on preoperative C-reactive protein (CRP), lymphocyte count, and serum albumin level, while an IBI was based on CRP and neutrophil-to-lymphocyte ratio. The prognostic value of IINS and IBI was assessed using univariate and multivariate Cox regression and Kaplan-Meier survival curves. The concordance index and calibration curve were used for internal validation of models. Decision curve analysis, net reclassification index and integrated discrimination improvement were used to compare the predictive performance of the models with traditional staging systems. Results: IINS and IBI were able to predict poor prognosis in HCC patients after hepatectomy, and a nomogram based on the IINS predicted survival at 1, 3, and 5 years better than other models or traditional staging systems. Conclusion: IINS may be accurate predictors of survival in HCC patients after hepatectomy, with potentially greater prognostic value than conventional markers.

Purpose Despite immune checkpoint inhibitor (ICI) has recently taken on an extremely important role in tumors, only a minority of hepatocellular carcinoma (HCC) patients are effective. The clinical value of PRC1 and DLGAP5 in HCC and its relationship with immune microenvironment have been rarely reported. Methods Key genes related to doubling time of HCC tumors were identified using WGCNA, and their expression was analyzed against our in-house RNA sequencing database, the Gene Expression Omnibus and the Cancer Genome Atlas database. We explored correlations between key genes and the immune microenvironment based on the TISCH and TIMER database, as well as clinicopathological characteristics and prognosis of HCC in patients at our center. Results WGCNA identified PRC1 and DLGAP5 as key genes in HCC. PRC1 and DLGAP5 were over-expressed in HCC tissues relative to normal tissues based on analysis of 2,154 patients and 1,344 controls. The genes gave respective areas under the summary receiver operator characteristic curve of 0.95 (95%CI 0.93–0.97) and 0.94 (95%CI 0.92–0.96). High expression of PRC1 and DLGAP5 positively correlated with tumor recurrence and microvascular invasion, was an independent risk factor for poor overall survival. PRC1 and DLGAP5 were co-expressed in proliferative T cells over-expressing immunosuppressive markers PDCD1, CTLA4, HAVCR2, LAG3 and TIGIT based on single-cell RNA-sequencing datasets. Conclusions PRC1 and DLGAP5 significantly upregulated in HCC are associated with poor prognosis and show strong diagnostic potential. PRC1 or DLGAP5 combined with CD8 T cell markers may serve as predictive biomarkers for the efficacy of ICI combination therapy.