IntroductionHepatocellular carcinoma (HCC) is the most common primary liver cancer with a low 5-year survival rate. The heterogeneity of HCC makes monotherapy unlikely. The development of diagnostic programs and new treatments targeting common genetic events in the carcinogenic process are providing further insights into the management of HCC. The aim of this study was firstly to validate key genes that are involved in promoting HCC development and as biomarkers for early diagnosis and, secondly, to define their links with antitumor immunity including inhibitory checkpoints.MethodsMultiple databases including Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier Plotter, UALCAN, and Oncomine were used for target gene screening and establishment of a co-expression network. Clinical data and RNAseq of 367 HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. The diagnostic and prognostic value of screened genes were tested by receiver operating characteristic (ROC) curve and correlation analysis. The links with the key genes in HCC and antitumor immunity were defined using both blood and liver tissue collected prospectively from HCC patients in our center.ResultsUpregulation of CCNB1, CDC20, and CENPF was commonly observed in HCC and are involved in the p53 signal pathway. The hepatic mRNA expression levels of these three genes were strongly associated with patients’ prognosis and expressed high value of area under the ROC curve (AUC). Further analysis revealed that these three genes were positively correlated with the gene expression levels of IFN-γ, TNF-α, and IL-17 in peripheral blood. In addition, the expression of CENPF showed positive correlation with the percentage of CD8pos T cells and negative correlation with the percentage of CD4pos T cells in the peripheral blood. In the HCC microenvironment, the transcript levels of these three genes and inhibitory checkpoint molecules including PD-1, CTLA-4, and TIM-3 were positively correlated.ConclusionThe upregulation of CCNB1, CDC20, and CENPF genes was a common event in hepatocarcinogenesis. Expression levels of CCNB1, CDC20, and CENPF showed potential for early diagnosis and prediction of prognosis in HCC patients. There is a close association between three genes and Th1/Th17 cytokines as well as the count of CD4pos and CD8pos T cells. The positive correlation between the three genes and inhibitory checkpoint genes, PD-1, CTLA-4, and TIM-3, indicates that these genes are linked with weakened antitumor immunity in HCC. Our findings may provide further insights into developing novel therapies for HCC.

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Introduction Globally, C. trachomatis is the leading infectious cause of blindness. There is evidence to suggest that trachomatous inflammation may be linked to ocular infection with other pathogenic organisms. Methods Conjunctival swab samples from 472 Tanzanian children who participated in a 4-year longitudinal study were analysed using optimised duplex qPCR assays to assess carriage of H. influenzae, CNS, S. pneumoniae and Adenovirus spp. in each sample. The presence of C. trachomatis (Ct) in the conjunctiva had previously been recorded. Logistic regression analysis, adjusted for age and sex, was performed to identify associations between the prevalence of bacterial infection and (1) progressive scarring trachoma, and (2) active trachoma (defined as the presence of follicular trachoma (TF) or trachomatous inflammation (TI)). Results Logistic regression identified no significant associations between (1) progressive scarring trachoma and Ct;and (2) progressive scarring trachoma and non-chlamydial bacterial infection. Active trachoma was only associated with conjunctival infection with H. influenzae. Logistic regression found that patients with ocular H. influenzae infection were more likely to demonstrate clinically-graded active trachoma (TF + TI) (OR = 1.96, 95% CI: 1.11 – 3.56, p = 0.023). Individual analyses of TF or TI and their associations with H. influenzae found (1) a strong association between ocular H. influenzae infection and TF (OR = 2.21, p = 0.0095); (2) no association between ocular H. influenzae infection and TI (OR = 2.19, p = 0.19). Conclusion These results indicate that H. influenzae might contribute to the TF phenotype. TF is widely used to assess population levels of trachoma.