CDK1-SRC Interaction-Dependent Transcriptional Activation of HSP90AB1 Promotes Antitumor Immunity in Hepatocellular Carcinoma.

This study aimed to analyze multiomics data and construct a regulatory network involving kinases, transcription factors, and immune genes in hepatocellular carcinoma (HCC) prognosis. The researchers used transcriptomic, proteomic, and clinical data from TCGA and GEO databases to identify immune genes associated with HCC. Statistical analysis, meta-analysis, and protein-protein interaction analyses were performed to identify key immune genes and their relationships. In vitro and in vivo experiments validated the CDK1-SRC-HSP90AB1 network's effects on HCC progression and antitumor immunity. A prognostic risk model was developed using clinicopathological features and immune infiltration. The immune genes LPA, BIRC5, HSP90AB1, ROBO1, and CCL20 were identified as the key prognostic factors. The CDK1-SRC-HSP90AB1 network promoted HCC cell proliferation and migration, with HSP90AB1 being transcriptionally activated by the CDK1-SRC interaction. Manipulating SRC or HSP90AB1 reversed the effects of CDK1 and SRC on HCC. The CDK1-SRC-HSP90AB1 network also influenced HCC tumor formation and antitumor immunity. Overall, this study highlights the importance of the CDK1-SRC-HSP90AB1 network as a crucial immune-regulatory network in the HCC prognosis.

TLR3 gene polymorphisms in cancer: a systematic review and meta-analysis.

INTRODUCTION: Recent studies examining the association of Toll-like receptor 3 (TLR3) gene polymorphisms with the risk of developing various types of cancer have reported conflicting results. Clarifying this association could advance our knowledge of the influence of TLR3 single nucleotide polymorphisms (SNPs) on cancer risk. METHODS: We systematically reviewed studies that focused on a collection of 12 SNPs located in the TLR3 gene and the details by which these SNPs influenced cancer risk. Additionally, 14 case-control studies comprising a total of 7997 cases of cancer and 8699 controls were included in a meta-analysis of 4 highly studied SNPs (rs3775290, rs3775291, rs3775292, and rs5743312). RESULTS: The variant TLR3 genotype rs5743312 (C9948T, intron 3, C>T) was significantly associated with an increased cancer risk as compared with the wild-type allele (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.00-1.24, P=0.047). No such association was observed with other TLR3 SNPs. In the stratified analysis, the rs3775290 (C13766T, C>T) variant genotype was found to be significantly associated with an increased cancer risk in Asian populations. Additionally, the rs3775291 (G13909A, G>A) variant genotype was significantly associated with an increased cancer risk in Asians, subgroup with hospital-based controls, and subgroup with a small sample size. CONCLUSION: After data integration, our findings suggest that the TLR3 rs5743312 polymorphism may contribute to an increased cancer risk.

Pri-miR-34b/c rs4938723 TC heterozygote is associated with increased cancer risks: evidence from published data.

The promoter region of the microRNA pri-miR-34b/c has a potentially functional polymorphism, rs4938723, located in a typical CpG island. Studies of the association between pri-miR-34b/c rs4938723 polymorphism and risks of various cancers have had inconsistent results. We therefore conducted a meta-analysis of nine studies that included 6,036 cancer patients and 7,490 controls to address this association. Overall, this meta-analysis showed the pri-miR-34b/c rs4938723 TC heterozygote to be significantly associated with increased risk of overall cancers compared with the wild-type TT genotype (P = 0.010, odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.18). In stratified analysis, the TC heterozygote was significantly associated with increased cancers risks in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. The CC genotypes of rs4938723 were also associated with increased hepatocellular cancer risk but associated with decreased colorectal cancer risk in the stratification analysis by a single cancer type. Thus our meta-analysis suggests that the pri-miR-34b/c rs4938723 TC heterozygote contributes to increased overall cancer risks, as well as shown in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. This rs4938723 SNP showed an opposite tendency orientation between the hepatocellular cancer and colorectal cancer risks. Large-sample studies are needed to verify our findings.

Ischemic injury of the liver in a porcine model of cardiac death assessed by in vivo microdialysis.

This study aims to evaluate the ischemic injury of the liver in a porcine model of cardiac death assessed by in vivo microdialysis. A porcine model of cardiac death was established by the suffocation method. Metabolic indicators were monitored using the microdialysis technique during warm ischemia time (WIT) and cold ischemia time (CIT). Pathological changes in ischemic-injured livers were observed by haematoxylin-eosin staining. The predictive values of biochemical parameters regarding the liver donor were evaluated by receiver operating characteristic curve analysis. All statistical analyses were conducted using the SPSS 18.0 software (SPSS Inc, Chicago, Illinois, USA). The degree of warm ischemic injury of the livers increased with prolonged WIT. Serum glucose, glycerol, pyruvate, lactic acid levels and lactate-to-pyruvate (L/P) ratio increased gradually during WIT. Results from Pearson correlation analyses indicated that serum lactate level and L/P ratio were positively associated with the degree of warm ischemic injury of the livers. The degree of cold ischemic injury of the livers gradually increased after 12 h CIT. Serum glucose, lactic acid and L/P ratio achieved a peak after 6-8 h of CIT, but gradually decreased with prolonged CIT. The peak of glycerol occurred after 8 h of CIT, while no changes were found with prolonged CIT. Serum pyruvate level exhibited an increasing trend after 12 h CIT. Our results confirmed that serum glucose and lactate levels were negatively correlated with cold ischemic injury of the liver. However, serum glycerol and pyruvate levels showed positive correlations with cold ischemic injury of the liver. The liver donor was unavailable after 30 min WIT and 24 h CIT. The cut-off value of serum lactate level for warm ischemic injury of the livers was 2.374 with a sensitivity (Sen) of 90 % and specificity (Spe) of 95 %; while the L/P radio was 0.026 (Sen = 80 %, Spe = 83 %). In addition, the cut-off values of serum glucose, lactate, glycerol and pyruvate levels for cold ischemic injury of the livers were 0.339 (Sen = 100 %, Spe = 77 %), 1.172 (Sen = 100 %, Spe = 61 %), 56.359 (Sen = 100 %, Spe = 65 %) and 0.020 (Sen = 100 %, Spe = 67 %), respectively. Our findings provide empirical evidences that serum glucose, lactate levels and L/P ratio may be good indicators for the degree of warm ischemic injury of the livers after cardiac death; while serum glucose, lactate, glycerol and pyruvate levels may be important in predicting cold ischemic injury.