Metabolic reprogramming is an important cancer hallmark. However, the mechanisms driving metabolic phenotypes of cancer cells are unclear. Here, we showed that the interferon (IFN)inducible protein, viperin, drives metabolic alteration in cancer cells. Viperin was observed in various types of cancer and inversely correlated with the survival rate of patients with gastric, lung, breast, renal, pancreatic, or brain cancer. By generating viperin knockdown or stably expressing cancer cells, we showed that viperin, but not a mutant lacking its iron-sulfur cluster-binding motif, increased lipogenesis and glycolysis via inhibition of fatty acid -oxidation in cancer cells. In the tumor microenvironment, deficiency of fatty acids and oxygen as well as production of IFNs upregulated viperin expression via the PI3K/AKT/mTOR/HIF-1 and JAK/STAT pathways.Moreover, viperin was primarily expressed in cancer stem-like cells (CSCs) and functioned to promote metabolic reprogramming and enhance CSC properties, thereby facilitating tumor growth in xenograft mouse models. Collectively, our data indicate that viperin-mediated metabolic alteration drives the metabolic phenotype and progression of cancer.

Background/Aims Epstein-Barr virus (EBV) and Helicobacter pylori (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS). Methods Overall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively. Results EBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p<0.001). Multivariate analysis revealed that EBV infection alone (hazard ratio [HR], 0.362; 95% CI, 0.131 to 0.996; p=0.049) and lower third location (HR, 0.624; 95% CI, 0.413 to 0.943; p=0.025) were inversely correlated with overall survival. During median follow-up period of 72 months, overall survival rate was not significantly different between the EBV and HP coinfection group and others (97.6% vs 86.8%, log-rank p=0.144). In non-GCLS patients (n=920), overall survival rate was not significantly different between the EBV infection group and others (96.9% vs 86.4%, log-rank p=0.126). Conclusions EBV and HP coinfection is not an independent prognostic factor for gastric cancer. EBV infection status, regardless of HP infection, affects the clinicopathologic features of all types of gastric cancer. However, it does not lead to a significant difference in overall survival of non-GCLS patients.

Background/Aims: Real-time polymerase chain reaction (RT-PCR) is a fast and simple method for the simultaneous detection of clarithromycin (CLR) resistance and Helicobacter pylori. We evaluated the effectiveness of RT-PCR compared to that of the rapid urease test (RUT) and assessed its value in verifying CLR resistance.Methods: A total of 70 specimens with confirmed H. pylori infection in culture were enrolled and analyzed in this prospective study. All specimens were subjected to RT-PCR assay using fluorescence melting peak signals to detect H. pylori infection and CLR resistances caused by either A2142G or A2143G mutations in the 23S ribosomal RNA gene (23S rRNA). The results were compared to those of RUT and antimicrobial susceptibility culturing tests to investigate the efficacy of RT-PCR.Results: Among the 70 specimens analyzed, the positivity rate was 97.1% (68/70) with RT-PCR and 82.9% (58/70) with RUT. CLR resistance (minimum inhibitory concentration >1.0 μg/mL) was confirmed in 18.6% (13/70), and fluorescence melting curve analysis showed that 84.6% (11/13) had point mutations in 23S rRNA. Ten specimens had only A2143G mutation, and one specimen contained both A2142G and A2143G mutations.Conclusions: RT-PCR assay was found to be more efficient than RUT in detecting H. pylori infection and could effectively verify CLR resistance compared to the antimicrobial susceptibility culturing test. Considering the high sensitivity and accessibility of RT-PCR method, it could be used to easily detect CLR-resistant H. pylori, thus helping clinicians select suitable treatment regimen and improve the eradication rate.