Background This study aimed to determine the impact of co-infection of Clonorchis sinensis (CS) and hepatitis B virus (HBV) on the prognosis of patients with hepatocellular carcinoma (HCC) following hepatectomy. Methods The clinicopathological information of 946 patients with HCC following hepatectomy was retrospectively analyzed. The patients were divided into four groups depending on whether they had CS infection and/or HBV infection: double-negative group (infected with neither CS nor HBV), simple CS group (infected with only CS), simple HBV group (infected with only HBV), and double-positive group (co-infected with CS and HBV). Kaplan-Meier curves were used to evaluate the overall survival (OS) and recurrence-free survival (RFS), while log-rank tests were used to compare survival rates. Further, Cox regression was used to perform both univariate and multivariate survival analyses to identify variables linked to the prognosis of HCC. Results The median overall survival (OS) and recurrence-free survival (RFS) in the double-positive, simple CS, simple HBV, and double-negative groups were 27 months and 9 months, 20 months and 7 months, 44 months and 12 months, and 42 months and 17 months, respectively. The double-positive group’s 1-year, 3-year, and 5-year OS and RFS rates were 79.2% and 46.9%, 62.6% and 28.4%, 47.8%, and 12.2%, respectively. The simple CS group’s 1-year, 3-year, and 5-year OS and RFS rates were 86.3% and 41.5%, 56.5% and 27.7%, 50.2%, and 18.5%, respectively. The simple HBV group’s 1-year, 3-year, and 5-year OS and RFS rates were 89.8% and 56.0%, 72.5% and 30.5%, 63.8%, and 19.9%, respectively. The double-negative group’s 1-year, 3-year, and 5-year OS and RFS rates were 91.5% and 62.3%, 76.1% and 32.9%, 64.0%, and 22.4%, respectively. Further, according to a Cox multivariate analysis, tumor size (> 5cm), Edmonson grade (III-IV), BCLC-C stage, and tumor satellite focus were independent risk factors for RFS and OS in patients with HCC. Conclusion Patients with HCC and Clonorchis sinensis infection experience a poor prognosis after hepatectomy, regardless of whether they are co-infected with HBV.
Background: We investigated whether the degree of inflammation and fibrosis in para-carcinoma tissue can predict prognosis of patients with non-cirrhotic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after hepatectomy. We also explored the mechanisms through which inflammation and fibrosis might affect prognosis. Methods: Clinicopathological data were retrospectively analyzed from 293 patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2012 to 2017. Based on the Scheuer score system, patients were classified into those showing mild or moderate-to-severe inflammation and fibrosis. Rates of overall and recurrence-free survival were compared between the groups using Kaplan–Meier curves, and survival predictors were identified using Cox regression. Using tumor and para-tumor tissues from independent samples of patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2018 to 2019, we performed next-generation sequencing and time-of-flight cytometry (CyTOF) to examine the influence of inflammation and fibrosis on gene expression and immune cell infiltration. Results: In the analysis of the 293 patients, those with mild inflammation and fibrosis showed significantly better overall and recurrence-free survival than those with moderate-to-severe inflammation and fibrosis. Multivariate Cox regression confirmed that moderate-to-severe inflammation and fibrosis were independent risk factors for worse survival. RNA sequencing and CyTOF showed that more severe inflammation and fibrosis were associated with stronger invasion and migration by hepatocytes. In cancerous tissues, the biological processes of cell proliferation were upregulated, the signaling pathways promoting tumor growth were activated, the proportion of Th17 cells promoting tumor progression was increased, and CD8+ T cells expressed higher levels of PD-L1. In para-cancerous tissues, biological processes of immune response and cell chemotaxis were downregulated, and the proportion of tumor-killing immune cells was decreased. Conclusion: Worse inflammation and fibrosis in non-cirrhotic HBV-associated HCC is associated with worse prognosis, which may reflect more aggressive tumor behavior and an immunosuppressed, pro-metastatic tumor microenvironment.
The extra spindle pole bodies-like 1 (ESPL1) gene is associated with malignant biological behaviors in several tumors. Nevertheless, the correlation between hepatocellular carcinoma (HCC) and ESPL1 has not been determined. The present study analyzed the molecular function and prognostic value of ESPL1 in HCC. Patients and Methods: Samples from 121 HCCs and 119 adjacent normal tissue specimens were subjected to next-generation sequencing. Clinicopathological and genetic data of HCC patients in The Cancer Genome Atlas (TCGA) were also collected. ESPL1 expression was assessed in 20 pairs of HCC and normal liver specimens by qRT-PCR and immunohistochemistry (IHC). The prognostic value of ESPL1 expression was determined by Cox univariate and multivariate regression analyses. ESPL1-related co-expressed genes were evaluated by weighted gene co-expression network analysis (WGCNA). Processes and pathways involving ESPL1 in HCC were determined by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The prognostic values of hub genes were determined by joint effect survival analysis. Results: RNA-Seq, RT-qPCR and IHC showed that ESPL1 expression was significantly higher in HCC than in normal liver tissues. Increased ESPL1 expression, greater tumor size and advanced BCLC stage were independently prognostic of poorer overall survival; and increased ESPL1 and advanced BCLC stage were independently prognostic of poorer recurrence-free survival. WGCNA showed that the top 10 co-expressed genes associated with ESPL1 were GTSE1,
Studies of diabetic glomerular injury raise the possibility of developing useful early biomarkers and therapeutic approaches for the treatment of type 2 diabetic nephropathy (T2DN). In this study, it is found that FGF13 expression is induced in glomerular endothelial cells (GECs) during T2DN progression. Endothelial-specific deletion of Fgf13 potentially alleviates T2DN damage, while Fgf13 overexpression has the opposite effects. Mechanistically, Fgf13 deficiency results in improved mitochondrial homeostasis and endothelial barrier integrity in T2DN. Moreover, FGF13-sensitive alteration of Parkin safeguards mitochondrial homeostasis in endothelium of diabetic nephropathy via promotion of mitophagy and inhibition of apoptosis. Additionally, it is confirmed that the beneficial effects of Fgf13 deficiency on T2DN are abolished by endothelial-specific double deletion of Fgf13 and Prkn. The effects of Fgf13 deficiency on mitophagy and apoptosis via Parkin-dependent regulation may be distinct and separable events under diabetic conditions. These data show that the bifunctional role of Fgf13 deficiency in promoting mitophagy and inhibiting apoptosis through Parkin can shape mitochondrial homeostasis regulation in GECs and T2DN progression. Acting as a potential therapeutic target for prevention and control of T2DN, mechanistically understanding of the biofunction of FGF13 may also be of relevance to the pathogenesis of other FGF13- and Parkin-associated diseases
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