Identifying a Three-Gene Signature and Associated Drugs for Hepatitis B Virus-Related Hepatocellular Carcinoma Using Comprehensive Bioinformatics Analysis.

Liver cancer is one of the most common cancer forms and a significant contributor to global cancer-associated mortality. Hepatitis B virus (HBV) infection contributes enormously to HCC development and progression. Despite this, the molecular basis of liver tumorigenesis is not clear. This work focused on identifying the relevant genetic markers and available drugs for treating HBV-related HCC. Differentially expressed genes (DEGs) from HBV-related HCC samples and corresponding healthy samples were identified from GSE62232 and GSE121248 datasets from the GEO2R repository (Gene Expression Omnibus). The Venn diagram software screened the overlapping DEGs between these two datasets. The DEGs were functionally assessed using protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses by different bioinformatic methods, and hub genes were screened. Hub genes and related drugs were verified by the GEPIA2 (Gene Expression Profiling Interactive Analysis) web server and the Quartata Web online platform. Overall, 116 DEGs (88 up-regulated and 28 down-regulated) related to signal transduction and metabolic pathways were identified. The nine significant target hub genes were TOP2A, RRM2, DTL, ECT2, ASPM, ANLN, BUB1B, CCNB1, and CDK1. Moreover, one screened drug, Fostamatinib, was targeted to CDK1. Our study identified three genes and associated drugs as probable targets for studying HBV-related HCC.

Evaluation of minor drug-resistant viral variants in patients experiencing virological failure (VF) on a first-line regimen in Fujian Province by high-throughput sequencing.

BACKGROUND: It is largely unknown how frequently minor HIV drug-resistant variants at levels under limit of detection of conventional genotyping are present in patients experiencing virological failure (VF). Further, the clinical implications of minor drug-resistant variants at time of virologic failure are unknown. METHODS: Fifteen patients experiencing VF on a first-line regimen were evaluated by high-throughput sequencing and compared with the conventional Sanger genotype drug resistance detection method. RESULTS: NRTI drug resistant mutations (DRMs) were detected in a high proportion of subjects, with the most common being M184V and TAMs. Minor resistant mutations accounted for 19.27% of the total drug-resistant mutations in patients with VF. A mean of 1.7 additional mutations per subject were detected by high-throughput sequencing, the difference was statistically significant, and those additional low-abundance drug-resistant mutations increased the genotypic resistance scores in 10 of 11 subjects (90.9%). Among persons experiencing VF, minor variants possessing major PI (protease inhibitor) DRMs were present in a minority of cases, which was also the case in ARV-naive subjects, and suggests PIs may be effective in subjects experiencing VF on subsequent second-line PI-based antiretroviral regimen. The high-throughput sequencing results of mutations between ART failure subjects and treatment naïve subjects were also compared. Three novel mutations were then screened with higher frequencies in the ART failure subjects. CONCLUSIONS: It is important to guide the replacement of treatment programs and screening for new drug-resistant mutation sites, and the use of high-throughput sequencing methods can more comprehensively study the characteristics of drug-resistant viral variants of patients experiencing VF on a first-line regimen.

[Genetic subtype and epidemiological feature of HIV-1 circulating strains among recently infected patients in Fujian province].

OBJECTIVE: In order to evaluate the distribution of genetic subtypes and epidemiological feature of HIV-1 circulating strains in Fujian province. METHODS: Blood samples and epidemiological data were collected from 104 newly infected patients who were distinguished by BED-CEIA methodology, during 2011-2012. Viral sequences(n = 81) of HIV-1 gag, env, and pol segments were amplified by nested PCR. RESULTS: Subtypes B and four Circulating Recombinant Forms, (CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B) were found in the samples, CRF01_AE(45.68%)and CRF07_BC(35.80%) were the two main HIV-1 strains in Fujian province. Compared with previous data, the proportion of CRF07_BC rose significantly while it gradually decreased in CRF01_AE. Heterosexual contact was still the principal transmission route in Fujian province, but the number of infection among men-who-have-sex-with- men grew rapidly. CONCLUSION: Results from this study suggested that different subtypes of HIV-1 strain existed in Fujian province. The distribution of subtypes and the mode of transmission were changing with the progress of epidemic. Dynamic monitoring of the molecular epidemiology trends of HIV-1 infection should be enhanced.