Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.

The vascular endothelial growth factor (VEGF) receptor tyrosine kinase subtype kinase insert domain receptor (KDR) contains seven extracellular Ig-like domains, of which the three most amino-terminal contain the necessary structural features required for VEGF binding. To clarify the functional role of KDR Ig-like domains 4-7, we compared VEGF-induced signaling in human embryonic kidney and porcine aortic endothelial cells expressing native versus mutant receptor proteins in which Ig-like domains 4-7, 4-6, or 7 had been deleted. Western blotting using an anti-receptor antibody indicated equivalent expression levels for each of the recombinant proteins. As expected, VEGF treatment robustly augmented native receptor autophosphorylation. In contrast, receptor autophosphorylation, as well as downstream signaling events, were VEGF-independent for cells expressing mutant receptors. 125I-VEGF 165 bound with equal or better affinity to mutant versus native receptor, although the number of radioligand binding sites was significantly reduced because a significant percentage of mutant, but not native, receptors were localized to the cell interior. As was the case for native KDR, 125

ObjectiveIncreased serum amyloid A (SAA) levels have been investigated in various human malignancies, but a consistent perspective has not been established to date. This study systematically reviewed the association between SAA levels and cancers.MethodsCochrane Library, PubMed and Embase were carefully searched for available studies. The following keywords were used in database searches: ‘serum amyloid A’, ‘SAA’, ‘cancer’, ‘tumour’, ‘carcinoma’, ‘nubble’, ‘knurl’ and ‘lump’. Pooled standard mean differences (SMDs) with corresponding 95% CIs were calculated using random-effects model analysis.ResultsTwenty studies, which contained 3682 cancer cases and 2424 healthy controls, were identified in this systematic review and meta-analysis. Our study suggested that the average SAA concentrations in the case groups were significantly higher than those in control groups (SMD 0.77, 95% CI 0.55 to 1.00, p<0.001). Subgroup analysis revealed that continent, age and cancer location were associated with SAA level differences between case groups and control groups. Sensitivity analyses showed the robustness and credibility of our results. In addition, we further stratified analyses for cancer stages and found that the concentrations of SAA increased gradually with the aggravation of cancer stages.ConclusionHigh circulating SAA levels were markedly associated with the developing risks of cancer, especially for participants from Asia, Oceania and Europe, or subject age more than 50, or locations in oesophageal squamous cell, ovarian, breast, lung, renal and gastric cancers. In addition, our study found that the concentrations of SAA increased with the severity of cancer stages.

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